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

Browse trials for

• Lung Neoplasms 7,243
• Neoplasms 9,365

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,557 are open to participants now.

This study's enrollment of 40 is below the median of 189 across 1,514 observational studies indexed under Lung Neoplasms.

Lead sponsor

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's is the lead sponsor of 25 studies on the registry; none are open to participants now.

Study population

Groups and 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

  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

• OtherCirculating tumour DNA (ctDNA)

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

Primary outcomes

1. 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.

   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)

2. 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

   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)

3. 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.

   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)

Secondary outcomes

1. 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

   This will be reported as frequency counts and proportions.

   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)

2. To determine the percentage of stage III patients with clinically relevant (targetable or prognostic), at any stage of lung cancer, ctDNA genetic alterations.

   Will be reported as frequency counts and proportions.

   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)

Publications

• 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. PubMed 35124411 ↗

Individual participant data

Plan to share: No