Clinical trial NCT03986463: CIrculating Tumour DNA in Lung Cancer (CITaDeL): Optimizing Sensitivity and Clinical Utility
Official title: CIrculating Tumour DNA in Lung Cancer (CITaDeL): Optimizing Sensitivity and Clinical Utility
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Lung Neoplasms
Lung Cancer
Neoplasm of Lung
Non Small Cell Lung Cancer
Lead sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Sponsor class: OTHER
First posted: 2019-06-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients receiving treatment at the London Regional Cancer Program in London, Ontario, Canada.

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.

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

Cohort 1

1. Stage III NSCLC as per the American Joint Committee on Cancer 8th edition (AJCC 8th ed.)
2. Appropriate to undergo concurrent chemotherapy and radiation
3. Planned radiation dose must be between 54 and 66 Gy
4. Chemotherapy regimen must include a platinum agent plus one of the following doublet agents: etoposide, pemetrexed, paclitaxel, vinorelbine, docetaxel, gemcitabine or vincristine
5. Day 1 platinum dose must be ≥ carboplatin 1.6 AUC or cisplatin 30 mg/m2
6. No prior system chemotherapy (induction) for their stage III NSCLC, any adjuvant chemotherapy given for resected disease must have been at least 100 days prior to enrollment

Cohort 2

1. Stage IV NSCLC or stage III NSCLC, as per the AJCC 8th ed.
2. Planning to start systemic cytotoxic chemotherapy, without concurrent radiation
3. Previous treatment with tyrosine kinase inhibitors or immunotherapy (PD-1, PD-L1, CTLA4 directed antibodies) is allowed as long as no cytotoxic chemotherapy was given concurrently
4. Previous palliative radiation is permitted, but must have been completed at least at least 21 days prior to the initiation of treatment
5. Chemotherapy regimen must include a platinum agent plus one of the following doublet agents: etoposide, pemetrexed, paclitaxel, vinorelbine, docetaxel, gemcitabine or vincristine
6. Day 1 platinum dose must be ≥ carboplatin 1.6 AUC or cisplatin 30 mg/m2
7. If cytotoxic chemotherapy was previously given for adjuvant or stage III NSCLC it must have been at least 100 days prior to enrollment

Cohort 3

1. Patients with advanced NSCLC set to undergo palliative radiation to the primary or regional or distant metastatic lesion(s), including intracranial lesions
2. Radiation dose scheduling must be 2.5 to 4.0 Gy on days 1 through 3 for extracranial treatment, ideally 40 Gy in 15 fractions, 20 Gy in 5 fractions, or 30 Gy in 10 fractions.
3. Radiation dose for brain lesions must be 6 to 9 Gy per dose, ideally 30 to 35 Gy in 5 daily fractions or 27 Gy in 3 fractions on alternating days
4. No plans for concurrent chemotherapy to be given
5. Five patients in cohort 3 will receive radiation to the primary tumor and five patients will receive radiation to brain lesions

Exclusion Criteria:

* Any other malignancy in the last five years other than adequately treated non-melanoma skin cancer

Primary outcomes:
measure: To measure the change in quantitative ctDNA levels following the initiation of cytotoxic chemotherapy or radiation
timeFrame: 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)
measure: To identify the timepoint after the initiation of treatment at which the quantified level of ctDNA peaks
timeFrame: 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)
measure: To detect genetic alterations at the time point of maximal ctDNA that were not present in baseline testing
timeFrame: 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)
Secondary outcomes:
measure: 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
timeFrame: 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)
measure: To determine the percentage of stage III patients with clinically relevant (targetable or prognostic), at any stage of lung cancer, ctDNA genetic alterations.
timeFrame: 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)
Other outcomes:
Locations:
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
Study officials:
References:
citation: Breadner DA, Vincent MD, Correa R, Black M, Warner A, Sanatani M, Bhat V, Morris C, Jones G, Allan A, Palma DA, Raphael J. Exploitation of treatment induced tumor lysis to enhance the sensitivity of ctDNA analysis: A first-in-human pilot study. Lung Cancer. 2022 Mar;165:145-151. doi: 10.1016/j.lungcan.2022.01.013. Epub 2022 Jan 29.