Clinical research in lung cancer and mesothelioma
The TOGA clinical trial and research program spans early and advanced non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), mesothelioma, other thymic malignancies, supportive & palliative care and translational research. Successful collaborations for clinical trials have been established within Australia and in North America, Asia and Europe. TOGA has a long-standing collaboration with the National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC) that has provided exemplary conduct of their clinical trials both locally, and internationally.
Research Development
TOGA seeks to endorse high-quality thoracic cancer clinical research to increase lung cancer research capacity, to provide peer-review to maximise feasibility and scientific merit and to maximise collaborations between the multiple disciplines involved in the treatment of thoracic cancers.
Endorsed proposals enable the use of the TOGA logo on research applications and TOGA will promote your research across their communications platforms where feasible.
Clinical research proposals are reviewed at working groups, which are conducted approximately four times per year. In advance of a working group meeting, TOGA will call for proposals via membership newsletters and social media. Following working group meetings, the TOGA Scientific Committee will approve endorsement of a research proposal.
Access additional resources and read more about TOGA’s research development and endorsement process.
Clinical trials open to recruitment
Title: ASPIRATION- An observational cohort study to assess the clinical impact of comprehensive genomic profiling in metastatic lung cancer patients
Study design: Observational cohort study
Indication: Newly-diagnosed metastatic non-squamous non small cell lung cancer (NSCLC)
Intervention: Comprehensive genomic profiling to identify actionable biomarkers to guide therapy
Summary: The ASPiRATION study is investigating the clinical impact of comprehensive genomic profiling (CGP) on the management of metastatic NSCLC and assessing the feasibility of CGP implementation nationally.
In Australia, standard of care tumour testing for lung cancer patients has the ability to identify changes in three genes: EGFR, ALK & ROS1, for which drugs are available on the Pharmaceutical Benefits Scheme (PBS).
If a patient is suitable for ASPiRATION, their tumour will also be tested using CGP, often referred to as molecular screening and/or profiling. This technique allows treating clinicians to look at changes in hundreds of genes in a single test. After a patient’s tumour is tested, a report is sent to the referring oncologist with information on (i) Any genetic biomarkers that were identified in the tumour and (ii) The types of treatment that may be suitable.
It is hoped this research will determine whether additional molecular screening can be feasibly integrated into Australian clinical practice for patients with metastatic NSCLC.
Recruitment target: 1000
Status: Recruiting
More information:
Supporting documents:
Information sheet for clinicians
Contact: MoST.study@sydney.edu.au
The ASPiRATION study is led by TOGA, in collaboration with Omico (Australian Genomic Cancer Medicine Centre) and the NHMRC Clinical Trials Centre (CTC).
ASPiRATION substudies include NSCLC-specific substudies and MoST substudies that cater for NSCLC patients with tumours expressing the appropriate molecular biomarkers. The ASPiRATION substudies are all Phase II single arm open label signal-seeking clinical trials with the intent to demonstrate or confirm drug activity and safety in order to inform subsequent randomised Phase III clinical trials.
Find sites that have opened ASPiRATION substudies
Title: 20/001 A single-arm, open-label, phase II trial of trastuzumab emtansine in patients with metastatic NSCLC harbouring HER2 mutations and/or amplifications detected using comprehensive genome profiling (CGP) (MoST 8)
Indication: Pathologically confirmed metastatic non-squamous NSCLC harbouring HER2 mutations and/or amplifications detected by comprehensive genome profiling in the ASPiRATION study
Intervention: Trastuzumab emtansine, 3.6mg/kg IV q3 weeks until disease progression or unacceptable toxicity.
Status: Open to recruitment
More information:
Title: 20/002 Single arm, open label, phase II trial of vemurafenib and cobimetinib in patients with advanced tumours harbouring BRAF V600 mutations detected by comprehensive genomic profiling (CGP) (MoST 12)
Indication: Patients with pathologically confirmed metastatic non-squamous NSCLC or other advanced cancers harbouring a BRAF V600 mutation detected by comprehensive genome profiling.
Intervention: Patients will receive continuous vemurafenib 960 mg twice a day (from days 1 to 28 in a 28-day cycle) in combination with cobimetinib 60 mg daily (from days 1 to 21 in a 28-day cycle, followed by a 7-day break in cobimetinib treatment from days 22 to 28) until disease progression, participant withdrawal or unacceptable toxicity.
Status: Open to recruitment
More information:
Title: 20/003 A single-arm, open-label, phase II trial of entrectinib in patients with advanced tumours harbouring NTRK fusions or ROS1 gene rearrangements detected by comprehensive genomic profiling (CGP) (MoST 13)
Indication: Patients with advanced cancers harbouring NTRK fusions or ROS1 gene rearrangements identified using CGP. NSCLC patients with
ROS1 gene alterations must be FISH-negative, i.e. not eligible for reimbursed ROS1-targeted treatment
Intervention: Patients will receive continuous entrectinib 600mg once daily orally until disease progression, participant withdrawal or unacceptable
toxicity.
Status: Open to recruitment
More information:
Title: 20/004 A single arm, open label, phase II trial of alectinib in patients with advanced tumours harbouring ALK gene alterations detected by comprehensive genomic profiling (CGP) (MoST 14)
Indication: Patients with advanced cancers harbouring ALK gene alterations identified using CGP. NSCLC patients with ALK gene alterations must be FISH-negative, i.e. not eligible for reimbursed ALK-targeted treatment
Intervention: Patients will receive continuous alectinib 600 mg twice a day until disease progression, participant withdrawal or unacceptable toxicity.
Status: Open to recruitment
More information:
Title: 20/008 A single-arm, open-label, signal-seeking, phase II trial of tepotinib in patients with advanced non-small cell lung cancer harbouring MET exon 14 skipping mutations detected by comprehensive genomic profiling (MoST 17)
Indication: pathologically confirmed metastatic non-squamous NSCLC harbouring METex14 skipping mutations detected by comprehensive genome profiling in the ASPiRATION study
Intervention: Tepotinib 500 mg daily until disease progression or unacceptable toxicity
Status: Open to recruitment
More information:
The ASPiRATION study is led by TOGA, in collaboration with Omico (Australian Genomic Cancer Medicine Centre) and the NHMRC Clinical Trials Centre (CTC).
Title: DREAM3R – DuRvalumab (MEDI4736) with chEmotherapy as first line treAtment in advanced pleural Mesothelioma – A phase 3 Randomised trial
Clinical trial design: Open-label Phase III randomised clinical trial
Indication: Newly diagnosed unresectable malignant pleural mesothelioma
Intervention: First-line treatment with standard chemotherapy of pemetrexed and cisplatin. Two-thirds of the participants in the study will be randomly assigned to also receive durvalumab (immunotherapy).
Summary: The DREAM3R clinical trial is determining the effectiveness of adding durvalumab to standard first line chemotherapy with cisplatin and pemetrexed in advanced malignant pleural mesothelioma and identifying potential and prognostic biomarkers from blood and tissue.
Durvalumab is an antibody (a type of human protein) that works by blocking a body substance called Programmed Death-Ligand 1 (PD-L1). Blocking PD-L1 helps the body’s immune system attack cancer cells. Research has shown that durvalumab can slow tumor growth and shrink tumors in some people with cancer. Previous studies of combining durvalumab and chemotherapy showed that this combination is active in advanced mesothelioma.
A recent amendment (2022) to this trial will enable patients randomised to standard of care to have a choice (made in consultation with the treating physician) that includes ipilimumab (ipi) and nivolumab (nivo), the dual immunotherapy combination on the PBS, rather than just chemotherapy alone. This combination immunotherapy targets a similar pathway to Durvalumab but using different targets. Ipi binds to CTLA-4 and nivo binds to PD1. This amendment means that mesothelioma patients on this clinical trial will have immunotherapy available in both arms.
It is hoped this research will demonstrate that durvalumab is safe and effective for the treatment of advanced mesothelioma, and that the results of this clinical trial will lead to improved outcomes for future mesothelioma patients.
Recruitment target: 480
Status: Recruiting
More information:
This study is a collaboration with PrECOG in the USA.
Contact: dream3r.study@sydney.edu.au
Title: SHERLOCK: Phase 2 trial of sotorasib in combination with carboplatin-pemetrexed and bevacizumab biosimilar as first line treatment for advanced non-squamous non-small cell lung cancer
with KRAS G12C mutation
Clinical trial design: Single-arm, phase 2 study with a safety run-in
Indication: Newly-diagnosed or recurrent metastatic non-squamous NSCLC with KRAS G12C mutation (treatment naive for advanced disease)
Intervention: All participants enrolled in this clinical trial will begin with Induction therapy of Sotorasib 960mg oral once daily, together with Carboplatin-Pemetrexed chemotherapy and Bevacizumab on day 1 every 3 weeks for 4 cycles.
Summary: The purpose of the study is to test the effectiveness of a new treatment combination for patients with non-small cell lung cancer (NSCLC) whose tumour has a specific type of gene mutation called KRAS G12C. This mutation is believed to cause the tumour to grow and spread. This study will investigate whether sotorasib used in combination with two chemotherapy drugs (called carboplatin and pemetrexed) and bevacizumab (which improves anti-cancer drug delivery), is well-tolerated, shrinks the tumour, delays relapse and provides longer and better quality of life.
Recruitment target: 52
Status: Recruiting
More information:
Contact: sherlock.study@sydney.edu.au
Clinical trials in follow up
Title: ALKTERNATE A single arm multi-centre translational proof of concept study investigating the safety and efficacy of alternating lorlatinib with crizotinib in a pre-treated advanced ALK-rearranged non small cell lung cancer (NSCLC) population with disease progression on a 2nd generation ALK tyrosine kinase inhibitor
Clinical trial design: Open-label Phase II single arm clinical trial
Indication: ALK-rearranged advanced NSCLC any number of lines of prior therapy with the immediately prior treatment a second generation ALK inhibitor
Intervention: All participants enrolled in this clinical trial will begin with Induction therapy which involves taking lorlatinib tablets every day for 12 weeks. Participants will then move onto the Alternating phase. During the Alternating phase participants will take crizotinib for 4 weeks, then lorlatinib for 8 weeks, then crizotinib for another 4 weeks, and lorlatinib for 8 weeks until disease progression or unacceptable side effects.
Summary: The primary purpose of this clinical trial is to evaluate the efficacy, safety and feasibility of alternating lorlatinib and crizotinib for the treatment of ALK-rearranged advanced NSCLC.
All participants enrolled in this clinical trial will begin taking lorlatinib tablets every day for 12 weeks. Participants will then move onto the Alternating phase. During the Alternating phase participants will take crizotinib for 4 weeks, then lorlatinib for 8 weeks, then crizotinib for another 4 weeks, and lorlatinib for 8 weeks until disease progression or unacceptable side effects. Following progression, some participants may be eligible to continue with alternating treatment or switch to continuous lorlatinib treatment until further progression, depending on whether your doctor believes that this would be of benefit to you.
All patients will be reviewed up to every four weeks clinically, with bloods tests, CT scan and MRI (brain) and side effect assessments.
It is hoped that the findings from this clinical trial will provide information on whether alternating treatment with crizotinib and lorlatinib is feasible, safe and effective for the treatment of ALK-rearranged advanced NSCLC with the potential to delay the emergence of drug resistance as compared to continuous lorlatinib therapy alone.
Recruitment target: 25
Status: Recruitment completed
More information:
Contact: malinda.itchins@sydney.edu.au
Title: ILLUMINATE A Phase 2 trial of durvalumab (MEDI4736) and tremelimumab with chemotherapy in metastatic EGFR mutant non-squamous non-small cell lung cancer (NSCLC) following progression on EGFR Tyrosine Kinase Inhibitors (TKIs)
Clinical trial design: Open-label Phase II clinical trial with two treatment cohorts (T790M+ve and T790M-ve)
Indication: Relapsed NSCLC with EGFR mutation of Exon 19 deletion or Exon 21 L858R point mutation and either:
- no evidence of T790M or
- T790M and progression on a 3rd generation TKI
Note that patients treated with > 2 lines of prior EGFR TKI or immunotherapy with checkpoint inhibitors are excluded from the study
Intervention: During induction, patients will receive 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 (or carboplatin AUC 5 if cisplatin is contraindicated), and pemetrexed 500mg/m2 via intravenous infusion every 3 weeks.
Immediately following induction, participants will commence a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks via intravenous infusion until disease progression or intolerance.
Summary: The primary purpose of this clinical trial is to evaluate the efficacy and tolerability of durvalumab and tremelimumab with platinum-pemetrexed in patients with metastatic EGFR-mutant NSCLC (T790M+ve or T790M-ve) following progression on EGFR Tyrosine Kinase Inhibitors.
All participants enrolled in this clinical trial will begin with induction therapy which involves 4 cycles of durvalumab 1500mg and tremelimumab 75mg with cisplatin 75mg/m2 or carboplatin AUC 5, and pemetrexed 500mg/m2 intravenously every 3 weeks.
Participants will then move into a maintenance phase of durvalumab 1500mg and pemetrexed 500mg/m2 once every 4 weeks until disease progression or unacceptable side effects.
All patients will be reviewed every three to four weeks by blood samples, CT scans and side effect assessments.
It is hoped that the findings from this clinical trial will provide information on whether treatment with durvalumab and tremelimumab with platinum-pemetrexed is feasible, safe and effective for the treatment of advanced EGFR NSCLC (T790M+ve or T790M-ve).
Recruitment target: Australia- 50 patients; Taiwan- 50 patients
Closed to recruitment in Australia: 18/11/21 (recruitment continues in Taiwan)
Final recruitment: Australia- 50 patients
More information:
Contact: illuminate.study@sydney.edu.au
Title: Phase 2 trial of alternating osimertinib with gefitinib in patients with EGFR-T790M mutation positive advanced non-small cell lung cancer
Clinical trial design: Single arm Phase II clinical trial
Indication: EGFR-T790M mutation positive advanced non-small cell lung cancer patients who have received prior therapy with an EGFR-TKI
Intervention: Osimertinib 80 mg daily for 8 weeks (Induction Phase).
Gefitinib 250 mg daily for 4 weeks then Osimertinib 80 mg daily for 4 weeks, and continue alternating (i.e. alternating 4 weekly cylces of each drug) until disease progression or unacceptable toxicity (Alternating Phase).
Following disease progression and if deemed appropriate by the treating Investigator, continuation of alternating therapy OR continuous Osimertinib 80 mg daily until further progression or unacceptable toxicity (Post-Progression Phase).
Summary: The primary purpose of this clinical trial is to measure the duration before progression when patients with EGFR-T790M mutation positive advanced non-small cell lung cancer are treated with osimertinib and gefitinib. It is hypothesised that alternating therapy with the gefitinib and osimertinib will modulate the populations of EGFR-T790M positive and negative tumour clones, delaying the emergence of resistance to osimertinib.
All participants enrolled in this clinical trial will begin with induction therapy which involves taking an osimertinib tablet once per day for eight weeks. Participants will then move onto the alternating phase, which involves alternating four-weekly cycles of treatment with gefitinib and osimertinib (i.e. four weeks gefitinib then four weeks osimertinib) until disease progression or unacceptable side effects. Following progression, some participants may be eligible to continue with alternating treatment or switch to continuous osimertinib treatment until further progression.
All patients will be reviewed up to every four weeks by blood samples, CT scans and side effect assessments.
Status: Follow up
Closed to recruitment: 12/6/19
Final recruitment number: 49
More information:
Contact: oscillate.study@sydney.edu.au
Title: Phase II trial to assess the overall survival benefit for patients with the use of Nivolumab and Ipilimumab in limited-stage small cell lung cancer (SCLC) after chemo-radiotherapy
Clinical trial design: Randomised open-label Phase II clinical trial
Indication: Untreated limited-stage SCLC
Intervention: During the induction phase patients will receive nivolumab at a dose of 1 mg/kg intravenously followed (on the same day) by ipilimumab at a dose of 3 mg/kg intravenously once every 3 weeks for 4 cycles. This is followed by the maintenance phase. During this phase patients will receive nivolumab 240 mg intravenously once every 2 weeks for a maximum of 12 months from start of maintenance phase (no minimum time for the maintenance phase).
Summary: Despite the fact that the majority of the patients with limited disease SCLC will respond very well to the standard treatment, a great proportion will relapse within 12 – 24 months.
Several studies in patients with lung cancer suggested a possible favourable association between the increased presence of immunologically active cells in the tumour and survival, suggesting a role for the host immune system. Nivolumab and ipilimumab are proteins that help your immune system to attack and destroy cancer cells.
The aim of the current clinical trial is to investigate the efficacy (how well the treatment works) and tolerability (how severe the side effects are) of the standard treatment (chemotherapy and radiotherapy) alone, compared with the standard treatment followed by nivolumab and ipilimumab in patients with limited SCLC.
Status: Follow up
Closed to recruitment: 29/4/19
Final recruitment number: 6
More information:
Contact: stimuli.study@sydney.edu.au
Title: NIVORAD – A randomised phase 2 trial of nivolumab and stereotactic ablative body radiotherapy in advanced non-small cell lung cancer, progressing after first or second line chemotherapy.
Clinical trial design: Randomised, controlled open-label clinical trial
Indication: Advanced non-small cell lung cancer, progressing after first of second line chemotherapy.
Intervention: Nivolumab 240mg (iv infusion) every 2 weeks plus a single fraction of SABR between days 8-14 of nivolumab cycle 1) Stereotactic Ablative Body Radiotherapy (SABR).
Summary: The aim of this clinical trial is to determine the activity and safety of treating a site of disease with with a single fraction of SABR during immunotherapy with nivolumab in advanced NSCLC progressing after 1 or 2 lines of chemotherapy.
Participants will be randomly allocated in a ratio of 2:1 to either nivolumab 240mg every 2 weeks plus SABR (experimental) or nivolumab 240mg every 2 weeks alone (control). Nivolumab is continued until disease progression or prohibitive toxicity.
Participants will be assessed regularly for treatment response and side effects during the treatment and follow up phase. Clinical assessments will be performed before each cycle of nivolumab (2 weekly) and CT scans at baseline, week 6, 12, 18, 24 then 12 weekly until progression. Anticancer treatments and survival will be reviewed every 12 weeks after progression. This will enable us to determine the activity and safety of each treatment option in patients with an asymptomatic metastasis.
Status: Follow up
Closed to recruitment: 7/6/19
Final recruitment number: 50
More information:
Contact: nivorad.study@sydney.edu.au
Title: A Randomized Trial of Durvalumab and Tremelimumab +/- Platinum-Based Chemotherapy in Patients With Metastatic (Stage IV) Squamous or Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Clinical trial design: Phase II randomised controlled clinical trial
Indication: First line treatment for Stage IV squamous or non-squamous NSCLC without the presence of known sensitizing EGFR mutations or known ALK-fusions
Intervention: Each patient will receive 1500 mg of durvalumab and 75 mg of tremelimumab given intravenously every 28 days for 4 cycles. This will be immediately followed by maintenance which includes 1500 mg durvalumab given intravenously every 28 days until progressive disease.
Summary: The purpose of this clinical trial is to compare the effects of an immunotherapy combination of both durvalumab plus tremelimumab with or without chemotherapy on you and your lung cancer.
Participants will be allocated by chance to one of two treatment groups. Participants in both groups will receive durvalumab and tremelimumab every 28 days for 4 cycles followed by durvalumab every 28 days until disease progression. Participants in one group only will also receive on of two types of chemotherapy during durvalumab and tremelimumab treatment. Patients with squamous cell NSCLC will receive gemcitabine and cisplatin or carboplatin chemotherapy, and patients with non-squamous NSCLC will receive pemetrexed and cisplatin or carboplatin chemotherapy.
Combining immunotherapy with chemotherapy is a promising new approach, with early results indicating much higher anti-cancer activity then would be expected with either treatment alone with no additional toxicity. The combination of two immunotherapy agents, with or without chemotherapy may be the best way to balance the chances of prolonged anticancer responses seen with immunotherapy against the risk of side-effects associated with treatment.
Status: Follow up
Closed to recruitment: 2/11/18
Final recruitment number: 53
More information:
Contact: br34.study@sydney.edu.au
Title: A Phase III Prospective Double Blind Placebo Controlled Randomized Study on the effect of Adjuvant MEDI4736 on Disease Free Survival In patients with Completely Resected Non-Small Cell Lung Cancer
Clinical trial design: Randomised, placebo-controlled double blind Phase III clinical trial
Indication: Stage IB-IIIA resected primary NSCLC
Intervention: 20mg/kg MEDI4736 (durvalumab) by intravenous infusion every 4 weeks for a maximum of 12 months.
Summary: The purpose of this clinical trial is to find out whether it is better to receive the new drug, MEDI4736, or no further treatment after surgery (and possibly chemotherapy) for lung cancer. The study involves randomly allocating participants to receive treatment with either MEDI4736 or placebo. Participants will be required to receive intravenous infusions of MEDI4736 or placebo (2:1 randomisation) at 20mg/kg every 4 weeks for 12 months. Participants will then be followed up for a maximum of 10 years to assess overall survival and disease free survival.
Status: Follow up
Closed to recruitment: 21/2/20
Final recruitment number: 114
More information:
Contact: br31.study@sydney.edu.au
Title: Efficacy of early referral to palliative care for improving quality of life and health care resources following recent diagnosis of advanced thoracic malignancies.
Clinical trial design: Phase III randomised, controlled clinical trial
Indication: Adults with advanced thoracic malignancy (non small cell lung cancer, small cell lung cancer or malignant pleural mesothelioma) that have been newly diagnosed within the last 60 days.
Intervention: Early referral to a hospital-based palliative care service for the specified palliative care intervention while receiving standard oncological care.
Summary: The primary purpose of this clinical trial is to evaluate whether early referral for palliative care can improve quality of life, cost effectiveness and quality of end of life care for adults who are newly diagnosed with advanced lung cancer.
All participants enrolled in this clinical trial will be randomly allocated (by chance) to receive either standard care referral to palliative care at the discretion of the treating oncologist, or to receive early referral to palliative care within 7 days of enrolling in this clinical trial. With the exception of the timing of the referral, the palliative care received by each group will be as per standard care, with information and care provided by the palliative care team as required for each participant.
Participants will be asked to complete a number of questionnaires relating to quality of life and cancer symptoms at regular time points. Carers will be asked to complete quality of life and death questionnaires and an interview at regular intervals.
It is anticipated that the findings from this clinical trial will provide information on whether early referral to palliative care following diagnosis of advanced lung cancer is beneficial for patient quality of life and end of life, and cost-effectiveness of care.
Status: Follow up
Closed to recruitment: 11/12/20
Final recruitment number: 113
More information:
Contact: pearl.study@sydney.edu.au
Endorsed clinical research
Title: CHEST RT: Chemotherapy and Immunotherapy in extensive stage small cell lung cancer with thoracic radiotherapy
Collaboration with: Trans Tasman Radiation Oncology Group (TROG) Trial 20.01
Clinical trial design: Single arm open label prospective multicentre Phase II clinical trial
Indication: Extensive Stage Small Cell Lung Cancer
Intervention: Durvalumab, chemotherapy (cisplatin/carboplatin and etoposide) and thoracic radiation therapy
Summary: CHEST RT is investigating the safety and effectiveness of combining chemotherapy and immunotherapy with chest radiation therapy for the treatment of extensive stage small cell lung cancer (ES-SCLC). For over 20 years, a combination of chemotherapy using etoposide with either cisplatin or carboplatin had been used to treat ES-SCLC. Adding immunotherapy to the chemotherapy combination has been shown to help boosts the body’s natural defences to fight cancer, improving response to treatment. This combination of chemotherapy with immunotherapy is now the standard of care treatment.
The immunotherapy used in this study is called durvalumab (IMFINZI). Durvalumab is approved by the Therapeutic Goods Administration (TGA) in Australia as the first-line treatment of patients with ES-SCLC, in combination with etoposide and either cisplatin or carboplatin.
Research has shown that radiation therapy also improves the ability of the immune system to recognise tumours. The researchers would like to investigate whether combining radiation therapy with the standard chemo/immunotherapy may further improve patients response to treatment.
Recruitment target: 35
More information:
Status: Recruiting
Contact: CHESTRT@trog.com.au
Title: Randomised phase II trial of Osimertinib with or without stereotactic radiosurgery for EGFR mutated NSCLC with brain metastases
Collaboration with: Trans Tasman Radiation Oncology Group (TROG) Trial 17.02
Study design: Phase II randomised, controlled, open label clinical trial
Indication: EGFR-mutation positive non-small cell lung cancer patients with brain metastases
Intervention: Upfront Stereotactic Radiosurgery (SRS) followed by 80mg Osimertinib taken once daily
Summary: 20-40% of patients with NSCLC will develop brain metastases at some point during their course of the disease. Osimertinib has demonstrated intracranial activity in EFGR mutated NSCLC with leptomeningeal disease in the phase 1 BLOOM study. Stereotactic radiosurgery (SRS) is one of the standard local treatment for patients with limited number of brain metastases. Currently, it is unclear whether adding SRS to Osimertinib will result in superior intracranial disease control in patients with EGFR mutated NSCLC with brain metastases diagnosed de novo or developed while on first line EGFR tyrosine kinase inhibitors (TKIs) such as Erlotinib and Gefinitib.
The aim of this clinical trial is to compare the effects of Osimertinib alone versus Osimertinib plus SRS on intra-cranial disease control in EGFR mutated NSCLC with brain metastases diagnosed or developed while on first line EGFR tyrosine kinase inhibitors.
Status: In follow up
Recruitment target: 80
More information:
Contact: OUTRUN@trog.com.au
Title: Conventional Care Versus Radioablation (Stereotactic Body Radiotherapy) for Extracranial Oligometastases (CORE)
Collaboration with: Trans Tasman Radiation Oncology Group (TROG) Trial 16.03
Study design: Phase II/III, multi-centre, non-blinded, parallel group randomised controlled clinical trial
Indication: Primary NSCLC who have presented with ≤3 extra-cranial, metachronous, oligometastases, all suitable for SBRT. Note that patients with primary breast or prostate cancer with the same criteria for oligometastases will also be recruited to this clinical trial.
Intervention: Stereotactic ablative radiotherapy (SABR)
Summary: Metastatic spread of cancer from its primary site to distant organs is the commonest cause of death from cancer. The term oligometastases describes an intermediate metastatic state, in which cancer exists as a limited number of metastases at first, before cells acquire the ability to metastasise more widely. For the large majority of solid cancers, once metastatic disease has been diagnosed the chances of cure are small. There are several situations where this is not the case, but it is not known if stereotactic body radiotherapy (SBRT) for oligometastatic disease will alter outcomes or whether the toxicity burden of this treatment is justified. SBRT is targeted radiotherapy which destroys cancer cells in the area of the body it is aimed at however low dose radiation may be received by surrounding tissue.
It is difficult to quantify incidence of patients with multiple primary cancers developing at intervals that are representative of oligometastatic stage IV disease, (defined for the purposes of this trial as ≤ 3 metastatic sites). However an increase in the use of surveillance imaging, together with improved diagnostic sensitivity has led to the diagnosis of patients with asymptomatic oligometastatic relapse becoming a more common clinical occurrence. The CORE study is a randomized controlled clinical trial that will be conducted in patients with cancer in one of three primary sites where oligometastatic disease relapse is a common clinical scenario: breast, prostate and non-small cell lung cancer (NSCLC). The clinical trial will evaluate the use of SBRT in this patient population.
Eligible patients who consent to participate in this clinical trial will be randomized to receive standard care or standard care plus SBRT.
Status: In follow up
Final recruitment: 245
More information:
Contact: CORE@trog.com.au
Title: Lung cancer screening for early detection
Collaboration with: Lead researcher: A/Prof Nicole Rankin, University of Melbourne
Summary: This research program will test ways of inviting and educating high-risk people about lung cancer screening. Lung cancer is the number one cause of cancer death worldwide. A screening test using low dose CT could save thousands of lives. The study will invite people, aged between 50 and 80 years and who smoke cigarettes daily or quit less than 15 years ago, via their family doctor.
Status: In progress
Title: DYNAMALK: ALK+ NSCLC: an Australian Dynamic ctDNA Profiling Study
Collaboration with: AURORA
Study design: Multi-centre, prospective non-interventional cohort study
Indication: ALK-mutation positive non-small cell lung cancer planned to initiate lorlatinib directly as next line of therapy as per Investigator’s discretion
Intervention: Collection of blood for real time ctDNA analysis at baseline, 6-12 weeks and 18 months
Summary: Eventual resistance to ALKi therapy remains inevitable. There is currently no predictive or prognostic biomarker accepted or available in routine clinical practice to guide the personalised management of advanced ALK+ cases from diagnosis and with each line of therapy, nor is there wide and timely accessibility of a ctDNA genomic panel to enable such molecular data in Australia.
DYNAMALK aims to undertake molecular profiling via an Australian ctDNA study in treatment naïve and pre-treated ALK+ patients to describe and correlate ctDNA findings according to any prior therapies and temporal genomic profiles of patients recruited, to identify patterns of emerging resistance against clinical outcomes, and to report the influence of ctDNA genomic data obtained real time in informing clinical management over and above standard of care.
Status: In start up
Recruitment target: 30
More information:
For patients
For clinicians
Contact: TBC
Title: Prevalence and correlates of self-reported cognitive function after systemic therapy for metastatic non-small cell lung cancer
Lead Researchers: Dr Maria Aslam and A/Prof Haryana Dhillon
Study design: Multi-centre, cross-sectional (descriptive) study of self-reported cognitive symptoms in Stage IV Non-small cell lung cancer patients in Australia and New Zealand.
Indication: Patients at least 3 months post diagnosis of Stage IV NSLC
Intervention: Observational study therefore no intervention
Summary: Cancer-related cognitive impairment is a well-recognised problem in cancer patients. However, there is little data that has assessed cognitive function in patients with metastatic disease, warranting further attention as a growing number of people are living with metastatic NSCLC.
To understand whether cognitive function is a problem for people who have received, chemotherapy, immunotherapy or targeted therapies, COGNITION aims to investigate self-reported cognitive symptoms in patients living beyond the first 3 months of diagnosis with stage IV NSLC.
Status: In progress
Recruitment target: 100
Title: Determining patterns of care and access to novel therapies for mesothelioma
Lead Researcher: Dr Susan Harden, Peter MacCallum Cancer Centre
Study design: A mixed method, co-designed project to create a short, bespoke experience of care and quality of life survey for mesothelioma.
Aim: To understand patterns of care and the use of immunotherapy in patients with malignant mesothelioma (MM). Furthermore, the study aims to collect the patient-reported experience of care and their quality of life to inform a learning health system model to drive patient-centred improvements in quality of care.
Summary: There are no available population-level clinical or patient-reported outcomes or treatment data for people living with mesothelioma in Victoria (or Australia). We do not know how many people are offered immunotherapy or other active treatments, nor do we have any insights into patient outcomes or their experiences of care. This research is designed to address this critically important unmet need.
Status: In progress
Recruitment target: 150 per annum
Title: RAPID series for night sweats in malignant mesothelioma
Lead Researcher: Dr Alannah Jackson and Prof Anna Nowak, Sir Charles Gairdner Hospital
Clinical trial design: A multi-centre, prospective consecutive cohort study. Data is collected by the clinician on day 0, day 7 and day 14 post-intervention commencement using a detailed custom data collection form.
Summary: There is a lack of robust evidence in the successful management of night sweats in patients with mesothelioma. As this is both a common and often debilitating symptom of their cancer, improving the evidence base for the pharmacological management of night sweats will be of great benefit to patients.
Recruitment target: 300
Status: In progress
Title: Enhancing Survivorship Care For Long-Term Responder Patients with Metastatic Non-Small Cell Lung Cancer (mNSCLC): Feasibility of a Multi-Disciplinary Team (MDT) Consultation
Lead Researchers: Dr Sarah Heynemann and Dr Steven Kao, Chris O’Brien Lifehouse
Clinical trial design: Phase 1, single-arm, prospective mixed-methods cohort study
Intervention: Multi-Disciplinary Team consultation
Summary: Previous work has demonstrated that patients with metastatic disease, including mNSCLC, who experience long periods of disease stability have unique survivorship challenges. It is unclear whether such survivorship needs are addressed by community clinicians.
The aim of this study is to facilitate and enhance communication between hospital-based cancer care teams, primary care clinicians and patients via the implementation of a multi-disciplinary team (MDT) consultation including both the patient’s GP and the patient to identify the survivorship concerns of individual long-term responder patients with mNSCLC and formulate a tailored survivorship care plan.
Recruitment target: 30
Status: In Progress
Title: The Ventilation Imaging for Thoracic Lung cancer radiation therapy (VITaL) trial
Lead researcher: Professor Paul Keall, The University of Sydney
Clinical trial design: A double-blind, prospective, randomised phase III clinical trial.
Indication: Stage I-III non-small lung cancer (NSLC) patients to be treated with curative intent with external beam radiotherapy (RT)
Intervention: Patients will be randomised between treatment with or without a plan that deliberately spares the high functioning lung, as measured by CT ventilation imaging, from high doses of radiation.
Summary: Radiation therapy (RT) is indicated for 77% of lung cancer patients. A common adverse event, affecting at least 20% of patients, is radiation-induced lung injury. To minimise radiation-induced lung injury, Professor Keall’s team has invented and pioneered ventilation imaging based on computed tomography (CT) which has been developed into a medical device (CIA). This medical device uses CT scans routinely acquired for planning RT to compute a CT ventilation map showing high functioning and low functioning lung regions.
VitAL aims to investigate whether the use of CIA can be used to direct radiation away from the healthy, high functioning regions towards the low functioning regions, thereby reducing toxicity and improving the patient’s quality of life.
Recruitment target: 130
Status: In Progress
Title: Cancer survivors experiencing Cancer-Related Fatigue: A study evaluating a combined Physical Activity and Mindfulness program (The ZENERGISE trial).
Lead Researcher: Dr Ashanya Malalasekera, NSW health
Clinical trial design: Step 1 is a pilot study testing feasibility of combined intervention to review outcomes and inform protocol accordingly. Step 2 is a randomised Phase 2 non-comparative / parallel 2-arm trial of the combined physical activity (PA) and mindfulness-based stress reduction (MBSR) intervention, and PA alone.
Indication: Patients who have initial cancer-related fatigue (CRF) score ≥4/10 (moderate to severe fatigue) and who will have completed primary adjuvant cancer treatment within the previous 6–60 months, with no evidence of recurrence.
Intervention: Combined online MBSR and PA intervention taking 3 hours per week.
Summary: Cancer Related Fatigue (CRF) is one of the most prevalent, persistent and distressing patient-reported symptoms associated with cancer and its treatment. Physical activity (PA) and psychosocial interventions targeted specifically for CRF have independently been shown to reduce CRF, with more robust evidence supporting PA. Mindfulness Based Stress Reduction (MBSR) is an emerging strategy to address a number of conditions, such as depression and Chronic Fatigue Syndrome.
The aim of this study is to determine if a combined PA and MBSR intervention is active in improving CRF in cancer survivors.
Recruitment target: 65
Status: In progress
Title: Improving response to immunotherapy in lung cancer
Lead Researcher: Dr Mara Zeissig, The Walter and Eliza Hall Institute
Summary: Approximately one third of lung adenocarcinomas are driven by mutations in the oncogene Kirsten Rat Sarcoma Virus (KRAS). Immunotherapy has improved survival outcomes compared with standard chemotherapy both as a monotherapy, and in combination with chemotherapy. Approximately 20% of KRAS mutant lung cancers do not respond to immunotherapy due to co-occurring mutations in other genes. To enhance response to immunotherapy, combination treatments tailored for these tumours are needed.
This research project aims to test whether using drugs specifically tailored to inhibit KRAS, in combination with immunotherapy in a laboratory setting, will provide evidence to suggest this approach is further assessed through clinical trials. This study also aims to identify novel drug targets to increase treatment options, and has the potential to identify new treatment regimens for improved survival in high-risk lung cancer patients.
Status: In progress
Title: Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance (TRACKER) project: characterising and overcoming resistance to immunotherapy in metastatic lung cancer
Lead Researcher: Dr Tracy Leong, Austin Health
Summary: This project will conduct early stage, small scale research, to assess the potential and feasibility of developing the first Australian Tissue Repository of Airway Cancers for Knowledge Expansion of Resistance (TRACKER) to address issues in translational lung cancer research. Since 2015, immunotherapy has emerged as a promising treatment, however 95% of patients will develop resistance. Conventional tissue sampling and analysis often means the opportunity to study mechanisms of immunotherapy resistance in tissue samples is not maximised.
This study aims to establish a clinically annotated biobank of tissue samples from patients with metastatic lung cancer that can be harnessed to advance knowledge in immunotherapy resistance. This will provide a platform for mechanism-driven therapeutic pre-clinical and clinical studies, to enhance personalised medicine approaches.
Status: In Progress
Title: Australian LUng Cancer clinical quality dAta Platform (LUCAP)
Lead Researcher: Professor Fraser Brims, Sir Charles Gairdner Hospital
Summary: LUCAP is a patient-focused research group who are developing a national clinical quality data platform for lung cancer that collects, analyses and reports on information such as how quickly people get lung cancer tests, what sort of tests are done and how quickly people get treatments. When large datasets are analysed, this real world data can provide an indication of quality of advances in lung cancer care.
Reports from this platform for individual lung cancer service providers can be compared against a set of national standards to inform of unwanted variation in care, and provide compelling evidence for this to be addressed. The platform can further extend to support innovative research in lung cancer care and treatments.
More information: LUCAP website
Status: In Progress
Title: The Victorian Lung Cancer Registry
Lead Researcher: Prof Rob Stirling, Clinical Registry Unit, Monash University
Summary: The Victorian Lung Cancer Registry is a Clinical Quality Registry established in 2011 and housed in the Clinical Registry Unit, Monash University. With governance oversight and nationally-based opt out ethical consent, the VLCR has recruited 44 hospitals from 19 health services representing over 85% of Victorian lung cancer diagnoses and registered 11,000 lung cancer patients providing both a Quality Indicator Report and an Annual Report to stakeholders with the objective of driving Quality Improvement through gap analysis and local on-site innovation.
More information: VLCR website
Status: In progress
Title: Australasian Landscape Survey of Lung Cancer Care
Lead Researcher: Prof Fraser Brims
Summary: This study aims to survey institutions treating lung cancer patients across ANZ regarding key workforce and infrastructure availability. Institutions will also be queried on access to contemporary and novel therapeutics, and other aspects of clinical care such as availability of MDT meetings, smoking cessation and access to clinical trials.
Status: In progress
Title: Patterns of Durvalumab Prescribing in Australia in patients with stage IIIB unresectable non-small cell lung cancer
Lead Researcher: Dr Udit Nindra
Summary: Currently the standard of care in unresectable stage III NSCLC is concurrent chemoradiotherapy followed by consolidation durvalumab. This is regardless of the patient’s PD-L1 expression or oncogenic driver mutation status.
This descriptive study employing a survey of current practices aims to determine patterns of Durvalumab prescribing in Australia in patients with EGFR-mt stage IIIB unresectable non-small cell lung cancer. The ultimate goal is to aid in standardising cancer care in Australia
Status: In Progress
Title: The BIG ISSUE breathlessness in lung cancer: making breathlessness management usual practice in lung cancer therapy.
Lead Researcher: De Meera Agar
Summary: Lung cancer patients expect to feel breathless, and little is done to implement therapies to address this symptom. Without management breathlessness negatively impacts physical function, social and psychological wellbeing. Despite there being evidence-based interventions to support people there remains a gap in implementation.
This project will investigate existing datasets and co-design a study to determine current practice and potentially lead to implementation research or clinical trials to improve the translation of research evidence to manage breathlessness in lung cancer patients.
Status: In Progress
Title: Immunotherapy ClinIcal DECIsion-making in Driver-nEgative, metastatic NSCLC. A Survey of Australian Medical Oncologists and Real World Analysis
Lead Researcher: De Samuel Smith
Summary: Immunotherapy has improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC) without an actionable driver mutation, when compared to chemotherapy alone. Since 2018 immunotherapy agents were approved for first-line use either as a single-agent immunotherapy (ICI) or in combination as chemoimmunotherapy (CIT) for patients with metastatic NSCLC and programmed death ligand-1 (PDL1) score greater than or equal to 50%.
The addition of chemotherapy to immunotherapy is hypothesised to improve the immunogenicity of the tumour micro-environment and induce a more rapid tumour response. However the addition of chemotherapy risks greater toxicity.
There remain a limited number of international real-world analyses that assess characteristics influencing treatment selection and none in the Australian setting. There are no descriptive analyses of current practice for this cohort in Australia.
This study aims to administer a survey to clinicians in order to understand current clinical practice and treatment decision-making for driver-negative, metastatic NSCLC with PDL1 50% or greater.
Status: In Progress
