Clinical trial NCT04258137: Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study
Official title: Circulating DNA to Improve Outcome of Oncology PatiEnt: A Randomized Study - COPE Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Colorectal Cancer
Non Small Cell Lung Cancer
Keywords: advanced
metastatic
liquid biopsy
genetic profiling
Lead sponsor: Institut Bergonié
Sponsor class: OTHER
First posted: 2020-02-06
Enrollment: 332
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: For each distinct population of patients with Advanced solid tumor (colorectal cancer and non-small-cell lung cancer), patients will be randomized between two arms:

Experimental procedure: initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up combining standard imaging and ctDNA analysis (subsequent MTBs at each radiological assessment).

Standard procedure: initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging.
Primary purpose: OTHER

Brief summary: COPE is a biology driven protocol with 2 independent, multicentric, two-arm non-comparative randomized (2:1) phase II trials in 2 distinct populations: colorectal cancer patients and non-small-lung cancer patients.

For each phase II trial, patient will be randomized between two arms with two patients randomized in arm A for one patient randomized in arm B:

* Arm A (Experimental - initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up combining standard imaging and ctDNA analysis)
* Arm B (Standard - initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging).

Detailed description: Primary tumor tissue, if accessible at all, does not always provide enough information to stratify individual patients to the most promising therapy. Re-analysis of metastatic lesions by needle biopsy is possible but invasive, and limited by the known intra-patient heterogeneity of individual lesions. These hurdles might be overcome by analyzing circulating tumor DNA (liquid biopsy), which in principle might reflect all subclones present at that specific time point and allow sequential monitoring of disease evolution.

Once tumor's genetic profiling is available, patients will be discussed within a multidisciplinary tumor board (MTB) which aims at discussing the genomic profiles and at providing a therapeutic decision for each patient. This MTB involves clinical oncologists, molecular biologists and clinical or biological project manager.

All the patients carrying an actionnable alteration will be proposed to receive a matched drug or to enter in a matched clinical trial depending on the possibility of inclusion at the time of molecular report.

the investigators hypothesize that implementing sequential circulating tumor DNA analysis can improve management of patients with advanced cancer and therefore their survival.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years,
2. Histology: colorectal cancer, non-small cell lung cancer,
3. Locally advanced/unresectable and/or metastatic solid tumor,
4. Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Appendix 1),
5. Measurable disease according to RECIST 1.1 (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1). At least one site of disease must be uni-dimensionally \> 10 mm,
6. No previous systemic treatment for advanced disease,
7. Availability of suitable paraffin embedded (FFPE) archive tumor material or at least one target lesion that can be biopsied for research purpose,
8. Eligible to first-line systemic therapy,
9. Patient with a social security in compliance with the French law,
10. Voluntary signed and dated written informed consent prior to any study specific procedure.

Exclusion Criteria:

1. Inability to swallow,
2. Major problem with intestinal absorption,
3. Previous allogeneic bone marrow transplant,
4. Previous or current malignancies of other histologies within the last 2 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin and prostate cancer,
5. Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV),
6. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in a clinical trial or which would jeopardize compliance with the protocol,
7. Individuals deprived of liberty or placed under guardianship,
8. Pregnant or breast feeding women,
9. Previous enrolment in the present study,
10. Any contraindication to first-line systemic therapy.

Primary outcomes:
measure: Assessment of cancer outcome in terms of overall survival (2 distincts population)
timeFrame: 18 months
Secondary outcomes:
measure: Proportion of patients with at least one actionable alteration (in 2 distincts populations)
timeFrame: Throughout the study: an average of 18 months
measure: Proportion of patients treated with a targeted therapy (in 2 distincts populations)
timeFrame: Throughout the study: an average of 18 months
Other outcomes:
Locations:
city: Bayonne
country: France
facility: Centre hospitalier de la Côte Basque
city: Bordeaux
country: France
facility: Clinique Tivoli-Ducos
city: Bordeaux
country: France
facility: Institut Bergonie
city: Bordeaux
country: France
facility: Polyclinique Bordeaux Nord Aquitaine
city: Brest
country: France
facility: CHRU Brest
city: Pau
country: France
facility: Polyclinique Marzet
Study officials:
References: