From Liquid Biopsy to Cure: Using ctDNA Detection of Minimal Residual Disease to Identify Patients for Curative Therapy After Lung Cancer Resection
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- University Health Network, Toronto
- Enrollment
- 66
- Locations
- 1
- Primary Endpoint
- Relapse Free Survival
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a study to look at whether the presence of circulating tumour DNA (ctDNA) in the blood can help to predict whether giving adjuvant treatment after surgery can decrease the chance of the cancer coming back in people with lung cancer.
Detailed Description
For people who have early stage non-small cell lung cancer (NSCLC), the usual treatment is surgery. For many people, surgery is enough to get rid of all the cancer. However, for some people, there may be a little bit of cancer remaining. If there is some cancer left over, it may lead to the cancer regrowing. This is called relapse. Many cancers shed little bits of their DNA (deoxyribonucleic acid, molecules that contain instructions for how cells develop and function) into the bloodstream. A blood test can be used to test for the amount of circulating tumour DNA (ctDNA). Some studies have shown that the presence of ctDNA in the blood may predict cancer recurrence. The purpose of this research study is to see if adjuvant treatment (additional treatment given after primary treatment) can help decrease the risk of the cancer recurring in people with lung cancer who have ctDNA detected in their blood after surgery.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years at the time of screening
- •Written informed consent obtained from the subject prior to performing any protocol-related procedures
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Weight ≥ 35 kg
- •Must have a life expectancy of at least 24 months
- •Complete surgical resection of T1-2N0M0 NSCLC or T3/T4 multifocal NSCLC
- •Any pathologic subtype of NSCLC is eligible, including adenocarcinoma and squamous carcinoma. Patients with targetable genomic alterations without approved or available targeted adjuvant therapy options are eligible
- •Patients with detectable plasma ctDNA before or after complete surgical resection are eligible (RaDaR TM assay, Inivata Morrisville, North Carolina, USA).
- •No prior chemotherapy or radiotherapy is allowed for the current diagnosis of resected NSCLC.
- •Adequate organ and marrow function as defined in Table 4 (3.1.1)
Exclusion Criteria
- Not provided
Arms & Interventions
Adjuvant chemo-immunotherapy therapy
All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead
Intervention: Nivolumab
Adjuvant chemo-immunotherapy therapy
All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead
Intervention: Pemetrexed
Adjuvant chemo-immunotherapy therapy
All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead
Intervention: Gemcitabine
Adjuvant chemo-immunotherapy therapy
All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead
Intervention: Cisplatin
Adjuvant chemo-immunotherapy therapy
All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead
Intervention: Carboplatin
Adjuvant chemo-immunotherapy therapy
All participants will have blood taken for ctDNA testing. A cycle is 21 days. Pemetrexed (for participants with non-squamous non-small cell lung cancer), intravenously (by vein) on Day 1 of Cycles 1-4, OR gemcitabine (for all other participants) on Days 1 and 8 of Cycles 1-4. Cisplatin\*, intravenously (by vein) on Day 1 of Cycles 1-4 Nivolumab, intravenously (by vein) on Day 1 of Cycles 1-4 \*If cisplatin is not tolerated, carboplatin may be given instead
Intervention: ctDNA blood test
Observation
All participants will have blood taken for ctDNA testing. Participants will be followed as per standard of care every 3 months.
Intervention: ctDNA blood test
Outcomes
Primary Outcomes
Relapse Free Survival
Time Frame: 2 years
To demonstrate the impact of intensified adjuvant therapy on relapse-free survival (RFS) in patients at high risk of relapse post-resection identified by pre- or post-operative detectable ctDNA plasma levels in patients with resected T1-T4 (T3-4 multifocal only) N0M0 NSCLC.
Secondary Outcomes
- Overall survival(3 years)
- Rate of ctDNA clearance(12 weeks)
- Number of adverse events(3 years)