Regorafenib With Low-dose Chemotherapies and Aspirin Followed by Standard Chemotherapies in Metastatic Colorectal Cancer

NCT05462613 | Recruiting Phase 2 DMC

• 1 other identifier: 2022/702
• Study Type: interventional
• Target: 446
• Locations: 1 country
• Sites: 16

Brief Summary

This study evaluates the interest of regorafenib in combination of metronomic chemotherapies and low-dose aspirin as a 2 months induction therapy before chemotherapy initiation in the second-line metastatic colorectal carcinoma

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• best objective response during treatment period (phase II)

  the best response rate evaluated with RECIST v1.1 criteria per an independent radiologist committee during the treatment period defined as the number of with complete response (CR) or partial response (PR) as best response divided by the total number of patients evaluable. Patients for whom best overall tumor response is not CR or PR will be considered non-responders.

  during treatment period (from first treatment administration and disease progression, an average of 14 months

• overall survival (OS) (phase III)

  Overall survival is defined as the time from the randomization to death from any cause.

  through study completion, an average of 64 months

Study Arms (2)

Experimental

EXPERIMENTAL

Regorafenib + metronomic Capecitabine + metronomic Cyclophosphamide + low-dose Aspirin followed by second line of chemotherapy (Bevacizumab + FOLFOX or FOLFIRI)

Other: quality of life questionnaires; Procedure: Blood sample; Drug: Regorafenib; Drug: Metronomic chemotherapies; Drug: Aspirin; Drug: Bevacizumab; Drug: FOLFIRI or FOLFOX

Control

ACTIVE COMPARATOR

Second line of chemotherapy (Bevacizumab + FOLFOX or FOLFIRI)

Other: quality of life questionnaires; Procedure: Blood sample; Drug: Bevacizumab; Drug: FOLFIRI or FOLFOX

Interventions

quality of life questionnaires OTHER

EORTC QLQ-C30 questionnaire (Quality of life questionnaire- Cancer 30) CR29 questionnaire (Colo-rectal cancer 29) EQ-5D3L questionnaire (EuroQol-5 Dimensions, 3 levels)

Control; Experimental

Blood sample PROCEDURE

Blood sample for plasma collection Blood sample for ctDNA (circulating tumoral DNA) collection

Control; Experimental

Regorafenib DRUG

\- Regorafenib will be administered 3 weeks out of 4 for two months or unacceptable toxicity. * For the first cycle: regorafenib will be administered according to the "REDOS" schedule (80 mg daily for week 1, 120 mg daily for week 2 and 160 mg daily for the third week of the first cycle). * For the second cycle: regorafenib will be administered at 160mg in the absence of significant toxicity during cycle 1 or at a 80/120mg daily dose according to toxicity observed with the last dose used in the first cycle.

Experimental

Metronomic chemotherapies DRUG

* Capecitabine: 625mg/m²/orally twice daily continuously during the first two months * Cyclophosphamide: 50 mg per os, daily, for two months

Experimental

Aspirin DRUG

75 mg orally and daily during two months

Experimental

Bevacizumab DRUG

5 mg/Kg every 2 weeks according to investigator practice, until disease progression or unacceptable toxicity

Control; Experimental

FOLFIRI or FOLFOX DRUG

every 2 weeks according to investigator practice

Control; Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically proven metastatic colorectal cancer in progression after a first line of chemotherapy +/- targeted therapy
• Patients must have been treated for their metastatic disease with one of the following regimens as first-line therapy:
• FOLFOX (Oxaliplatine, 5-Fluoro-uracil)
• FOLFIRI (Irinotecan, 5-Fluoro-uracil)
• FOLFIRINOX (Irinotecan, oxaplipatin, 5-Fluoro-uracil) or FOLFOXIRI (irinotecan, oxaliplatin, 5-Fluoro-uracil)
• FOLFOX and anti-VEGFA (bevacizumab only)
• FOLFIRI and anti-VEGFA (bevacizumab only)
• FOLFIRINOX or FOLFOXIRI and anti-VEGFA (bevacizumab only)
• FOLFOX and anti-EGFR (Epiderman Growth Factor Recepto)
• FOLFIRI and anti-EGFR
• FOLFIRINOX or FOLFOXIRI and anti-EGFR
• Of note, a chemotherapy prescribed for metastases occurring within six months after the end of an adjuvant chemotherapy are considered as a second line of therapy.
• Patients should have a history of resistance to first line chemotherapy defined by:
• Disease progression during the first line of their metastatic disease, less than 3 months after the last exposition to chemotherapy (even a chemotherapy regimen mentioned above or a 5-Fluoro-uracil-based maintenance therapy).
• Disease relapse within 6 months after the end of an adjuvant FOLFOX based chemotherapy.

You may not qualify if:

• Current participation in a study of an investigational agent. Patients might be included at least 21 days following the last investigational agent administration.
• Patient under judicial protection (curators, autorship) and/or deprived of freedom,
• Planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment,
• Previous exposure to regorafenib,
• Previous exposure to other anti-angiogenic treatment than bevacizumab,
• Complete deficit in dihydropyrimidine dehydrogenase (DPD),
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,
• Pregnant or breast-feeding subjects,
• Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2, unstable angina (anginal symptomatology at rest),
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months),
• Myocardial infarction less than 6 months before start of study drug,
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted),
• Uncontrolled hypertension (Systolic blood pressure \>150 mmHg and/or diastolic pressure \>100 mmHg despite optimal medical management), or history of hypertensive crisis, or hypertensive encephalopathy
• Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea),
• Ongoing infection \>grade 2 CTCAE V5 (Appendix 6 ),

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead

Study Sites (16)

CHU de Besançon

Besançon, France

RECRUITING

CHU Estain

Clermont-Ferrand, France

NOT YET RECRUITING

Hôpital Henri Mondor

Créteil, France

RECRUITING

Centre Georges François Leclerc

Dijon, France

RECRUITING

Centre Léon Bérard

Lyon, 69000, France

NOT YET RECRUITING

Hôpital Privé Jean Mermoz

Lyon, France

RECRUITING

Hôpital Nord Franche Comté

Montbéliard, France

RECRUITING

CHU Montpellier

Montpellier, France

RECRUITING

Groupe hospitalier de la région de Mulhouse et Sud Alsace

Mulhouse, France

RECRUITING

Centre Antoine Lacassagne

Nice, France

NOT YET RECRUITING

Hôpital Européen Georges Pompidou

Paris, France

RECRUITING

Hôpital la Pitié-Salpétrière

Paris, France

RECRUITING

Hôpital Saint antoine

Paris, France

RECRUITING

Institut Mutualiste Montsouris

Paris, France

RECRUITING

CHU de Reims - Hôpital Robert Debré

Reims, France

RECRUITING

Hôpital FOCH

Suresnes, France

NOT YET RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Blood Specimen Collection; regorafenib; Aspirin; Bevacizumab; Folfox protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Angélique VIENOT, MD, PhD

CONTACT

00 33 3 81 47 99 99; angelique.vienot@gmail.com

Christophe BORG, MD, PhD

CONTACT

00 33 3 81 47 99 99; xtoph.borg@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2022
• First Posted: July 18, 2022
• Study Start: May 9, 2023
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2030
• Last Updated: December 20, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)