COPE: Circulating DNA to Improve Outcome of Oncology PatiEnt. A Randomized Study

Sponsor

Institut Bergonié (Other)

Overall Status

Recruiting

CT.gov ID

NCT04258137

Collaborator

(none)

332

Enrollment

Locations

Arms

42.9

Anticipated Duration (Months)

55.3

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Non Small Cell Lung Cancer	Genetic: Liquid biopsy	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

332 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Circulating DNA to Improve Outcome of Oncology PatiEnt: A Randomized Study - COPE Study

Actual Study Start Date :

Sep 4, 2020

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Apr 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental procedure for colorectal cancer Patients with Advanced colorectal cancer will be managed by 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)	Genetic: Liquid biopsy Liquid biopsy will be performed at cycle 1 day 1 and cycle 2 day of each line of systemic treatment, at each tumor evaluation by Imaging and at confirmation of progression
No Intervention: Standard procedure for colorectal cancer Patients with Advanced colorectal cancer will be managedby initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging.
Experimental: Experimental procedure for non-small cell lung cancer Patients with Advanced non-small cell lung cancer will be managed by 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)	Genetic: Liquid biopsy Liquid biopsy will be performed at cycle 1 day 1 and cycle 2 day of each line of systemic treatment, at each tumor evaluation by Imaging and at confirmation of progression
No Intervention: Standard procedure for non-small cell lung cancer Patients with Advanced non-small cell lung cancer will be managed by initial MTB providing therapeutic recommendation based on tumor sequencing and then follow-up based on standard imaging.

Outcome Measures

Primary Outcome Measures

Assessment of cancer outcome in terms of overall survival (2 distincts population) [18 months]
Overall Survival (OS) is defined as the time interval between the date of randomization and the date of death (of any cause).

Secondary Outcome Measures

Proportion of patients with at least one actionable alteration (in 2 distincts populations) [Throughout the study: an average of 18 months]
An actionable alteration is determined according to the molecular tumor board.
Proportion of patients treated with a targeted therapy (in 2 distincts populations) [Throughout the study: an average of 18 months]
A profiling-based targeted therapy corresponds to a therapy targeting an actionable alteration

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years,
Histology: colorectal cancer, non-small cell lung cancer,
Locally advanced/unresectable and/or metastatic solid tumor,
Eastern Cooperative Oncology Group (ECOG) performance status < 2 (Appendix 1),
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,
No previous systemic treatment for advanced disease,
Availability of suitable paraffin embedded (FFPE) archive tumor material or at least one target lesion that can be biopsied for research purpose,
Eligible to first-line systemic therapy,
Patient with a social security in compliance with the French law,
Voluntary signed and dated written informed consent prior to any study specific procedure.

Exclusion Criteria:

Radiological evidence of symptomatic or progressive brain metastases,
Abnormal coagulation contraindicating biopsy,
Inability to swallow,
Major problem with intestinal absorption,
Previous allogeneic bone marrow transplant,
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,
Evidence of severe or uncontrolled systemic disease (uncontrolled hypertension, active bleeding diatheses, or active Hepatitis B, C and HIV),
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,
Individuals deprived of liberty or placed under guardianship,
Pregnant or breast feeding women,
Previous enrolment in the present study,
Any contraindication to first-line systemic therapy.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Centre hospitalier de la Côte Basque	Bayonne	France	64109
2	Clinique Tivoli-Ducos	Bordeaux	France	33000
3	Institut Bergonie	Bordeaux	France	33076
4	Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France	33077
5	CHRU Brest	Brest	France	29200
6	Polyclinique Marzet	Pau	France	64000