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

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ClinicalTrials.gov Identifier: NCT03986463
Recruitment Status : Completed
First Posted : June 14, 2019
Last Update Posted : February 18, 2021
Sponsor:
Information provided by (Responsible Party):
Lawson Health Research Institute

Tracking Information
First Submitted Date April 30, 2019
First Posted Date June 14, 2019
Last Update Posted Date February 18, 2021
Actual Study Start Date May 1, 2019
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 18, 2019)
  • 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.
Original Primary Outcome Measures
 (submitted: June 13, 2019)
  • 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 ]
    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 ]
    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 ]
    Will be reported as gene names, with allelic frequencies, found in post-treatment samples that were not present in samples collected at baseline.
Change History
Current Secondary Outcome Measures
 (submitted: June 18, 2019)
  • 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 [ 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 frequency counts and proportions.
  • To determine the percentage of stage III patients with clinically relevant (targetable or prognostic), at any stage of lung cancer, ctDNA genetic alterations. [ 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 frequency counts and proportions.
Original Secondary Outcome Measures
 (submitted: June 13, 2019)
  • 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 [ 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 ]
    This will be reported as frequency counts and proportions.
  • To determine the percentage of stage III patients with clinically relevant (targetable or prognostic), at any stage of lung cancer, ctDNA genetic alterations. [ 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 ]
    Will be reported as frequency counts and proportions.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title 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
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.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Circulating tumour DNA (ctDNA) will be isolated from blood samples and stored for potential future testing.
Sampling Method Non-Probability Sample
Study Population Patients receiving treatment at the London Regional Cancer Program in London, Ontario, Canada.
Condition
  • Lung Neoplasms
  • Lung Cancer
  • Neoplasm of Lung
  • Non Small Cell Lung Cancer
Intervention Other: Circulating tumour DNA (ctDNA)
Circulating tumour DNA (ctDNA) will be isolated from blood samples
Study Groups/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
    Intervention: 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
    Intervention: 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
    Intervention: Other: Circulating tumour DNA (ctDNA)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: February 17, 2021)
40
Original Estimated Enrollment
 (submitted: June 13, 2019)
30
Actual Study Completion Date December 31, 2020
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Canada
Removed Location Countries  
 
Administrative Information
NCT Number NCT03986463
Other Study ID Numbers CITaDeL
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Lawson Health Research Institute
Study Sponsor Lawson Health Research Institute
Collaborators Not Provided
Investigators Not Provided
PRS Account Lawson Health Research Institute
Verification Date August 2020