CIrculating Tumour DNA in Lung Cancer (CITaDeL): Optimizing Sensitivity and Clinical Utility
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Lung Neoplasms
- Sponsor
- Lawson Health Research Institute
- Enrollment
- 40
- Locations
- 1
- Primary Endpoint
- To measure the change in quantitative ctDNA levels following the initiation of cytotoxic chemotherapy or radiation
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a prospective observation study in patients with non-small cell lung cancer (NSCLC) starting either cytotoxic chemotherapy or radiation therapy. It will assess changes in circulating tumor DNA (ctDNA) in the days following the initiation of treatment, as well as longitudinal monitoring, to assess the dynamics and value of ctDNA in stage III-IV NSCLC.
Detailed Description
The study consists of three cohorts of patients initiating a new treatment for their NSCLC. The cohorts of (1) patients starting concurrent chemotherapy and radiation for stage III NSCLC (2) patients with advanced NSCLC starting cytotoxic chemotherapy (with or without pembrolizumab) (3) patients with advanced NSCLC starting palliative radiation therapy. This study aims to study the changes in ctDNA levels following a new treatment in lung cancer patients and to explore if the diagnostic utility of ctDNA testing is improved immediately following treatment when tumour cells are actively dying. It will also examine the changes in ctDNA levels and mutational analysis longitudinally.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically diagnosed NSCLC
- •Age 18 or older
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- •Patients must be able to provide informed consent
- •Patients must meet the criteria above AND fulfill the criteria below for entry into one of the 3 cohorts
- •Stage III NSCLC as per the American Joint Committee on Cancer 8th edition (AJCC 8th ed.)
- •Appropriate to undergo concurrent chemotherapy and radiation
- •Planned radiation dose must be between 54 and 66 Gy
- •Chemotherapy regimen must include a platinum agent plus one of the following doublet agents: etoposide, pemetrexed, paclitaxel, vinorelbine, docetaxel, gemcitabine or vincristine
- •Day 1 platinum dose must be ≥ carboplatin 1.6 AUC or cisplatin 30 mg/m2
Exclusion Criteria
- •Any other malignancy in the last five years other than adequately treated non-melanoma skin cancer
Outcomes
Primary Outcomes
To measure the change in quantitative ctDNA levels following the initiation of cytotoxic chemotherapy or radiation
Time Frame: Cohort 1 and 2: Baseline (pre-treatment) to end of cycle 1 (each cycle is 21 days) of chemotherapy. Cohort 3: Baseline (pre-treatment) to end of radiotherapy (up to 3 weeks)
Post-treatment ctDNA levels will be reported as the mean percent increase with standard deviation at maximum compared to baseline (pre-treatment) ctDNA levels.
To identify the timepoint after the initiation of treatment at which the quantified level of ctDNA peaks
Time Frame: Cohort 1 and 2: Baseline (pre-treatment) to end of cycle 1 (each cycle is 21 days) of chemotherapy. Cohort 3: Baseline (pre-treatment) to end of radiotherapy (up to 3 weeks)
This will be reported as the mean time to maximal ctDNA level with standard deviation from the initiation of treatment
To detect genetic alterations at the time point of maximal ctDNA that were not present in baseline testing
Time Frame: Cohort 1 and 2: Baseline (pre-treatment) to end of cycle 1 (each cycle is 21 days) of chemotherapy. Cohort 3: Baseline (pre-treatment) to end of radiotherapy (up to 3 weeks)
Will be reported as gene names, with allelic frequencies, found in post-treatment samples that were not present in samples collected at baseline.
Secondary Outcomes
- To identify the proportion of patients that do not have genetic alterations present in baseline samples but have genetic alterations detected at the timepoint of maximal quantified ctDNA(Cohort 1 and 2: Baseline (pre-treatment) to end of cycle 1 (each cycle is 21 days) of chemotherapy. Cohort 3: Baseline (pre-treatment) to end of radiotherapy (up to 3 weeks))
- To determine the percentage of stage III patients with clinically relevant (targetable or prognostic), at any stage of lung cancer, ctDNA genetic alterations.(Cohort 1 and 2: Baseline (pre-treatment) to end of cycle 1 (each cycle is 21 days) of chemotherapy. Cohort 3: Baseline (pre-treatment) to end of radiotherapy (up to 3 weeks))