CIrculating Tumour DNA in Lung Cancer (CITaDeL): Optimizi... | NCT03986463

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Description	Intervention Names
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	Other: Circulating tumour DNA (ctDNA)
Cohort 2	Stage IV NSCLC or stage III NSCLC, as per the AJCC 8th ed. Planning to start systemic cytotoxic chemotherapy, without concurrent radiation 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 Previous palliative radiation is permitted, but must have been completed at least at least 21 days prior to the initiation of treatment 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 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	Patients with advanced NSCLC set to undergo palliative radiation to the primary or regional or distant metastatic lesion(s), including intracranial lesions 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. 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 No plans for concurrent chemotherapy to be given Five patients in cohort 3 will receive radiation to the primary tumor and five patients will receive radiation to brain lesions

Name	Type	Description	Arm Group Labels	Other Names
Circulating tumour DNA (ctDNA)	Other	Circulating tumour DNA (ctDNA) will be isolated from blood samples	Cohort 1 Cohort 2 Cohort 3

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.	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)

Eligibility Module

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

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
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
Previous palliative radiation is permitted, but must have been completed at least at least 21 days prior to the initiation of treatment
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
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

Patients with advanced NSCLC set to undergo palliative radiation to the primary or regional or distant metastatic lesion(s), including intracranial lesions
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.
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
No plans for concurrent chemotherapy to be given
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

ID	Term
D008175	Lung Neoplasms
D002289	Carcinoma, Non-Small-Cell Lung

ID	Term
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms