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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Non Small Cell Lung Cancer
• Intervention / Treatment: Genetic: Liquid biopsy

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 Type: Interventional
• Enrollment (Anticipated): 332
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bayonne, France, 64109
    • Recruiting
    • Centre Hospitalier de la Côte Basque
  • Bordeaux, France, 33076
    • Recruiting
    • Institut Bergonié
  • Bordeaux, France, 33000
    • Recruiting
    • Clinique Tivoli-Ducos
  • Bordeaux, France, 33077
    • Recruiting
    • Polyclinique Bordeaux Nord Aquitaine
  • Brest, France, 29200
    • Recruiting
    • CHRU Brest
  • Pau, France, 64000
    • Recruiting
    • Polyclinique Marzet

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institut Bergonié

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): April 1, 2025

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): March 2, 2023
• Last Update Submitted That Met QC Criteria: March 1, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: metastatic; advanced; liquid biopsy; genetic profiling
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms
• Other Study ID Numbers: IB 2019-06; 2019-A02479-48 (Other Identifier: ANSM IDRCB Number); ML41112 (Other Identifier: Roche ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No