CIrculating Tumour DNA in Lung Cancer (CITaDeL): Optimizing Sensitivity and Clinical Utility

NCT03986463 | Completed

• 1 other identifier: CITaDeL
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Neoplasms; Lung Cancer; Neoplasm of Lung; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• To measure the change in quantitative ctDNA levels following the initiation of cytotoxic chemotherapy or radiation

  Post-treatment ctDNA levels will be reported as the mean percent increase with standard deviation at maximum compared to baseline (pre-treatment) ctDNA levels.

  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 identify the timepoint after the initiation of treatment at which the quantified level of ctDNA peaks

  This will be reported as the mean time to maximal ctDNA level with standard deviation from the initiation of treatment

  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 detect genetic alterations at the time point of maximal ctDNA that were not present in baseline testing

  Will be reported as gene names, with allelic frequencies, found in post-treatment samples that were not present in samples collected at baseline.

  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 (2)

• 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)

Study Arms (3)

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

Other: Circulating tumour DNA (ctDNA)

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

Other: Circulating tumour DNA (ctDNA)

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

Other: Circulating tumour DNA (ctDNA)

Interventions

Circulating tumour DNA (ctDNA) OTHER

Circulating tumour DNA (ctDNA) will be isolated from blood samples

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients receiving treatment at the London Regional Cancer Program in London, Ontario, Canada.

You may qualify if:

• 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
• 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
• 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
• Stage IV NSCLC or stage III NSCLC, as per the AJCC 8th ed.
• Planning to start systemic cytotoxic chemotherapy, without concurrent radiation

You may not qualify if:

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

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Related Publications (1)

• 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.

  PMID: 35124411 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Circulating tumour DNA (ctDNA) will be isolated from blood samples and stored for potential future testing.

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2019
• First Posted: June 14, 2019
• Study Start: May 1, 2019
• Primary Completion: December 31, 2020
• Study Completion: December 31, 2020
• Last Updated: February 18, 2021

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)