Assessing a Regorafenib-irinotecan Combination Versus Regorafenib Alone in Metastatic Colorectal Cancer Patients

NCT03829462 | Active Not Recruiting Phase 3 Results DMC

• 1 other identifier: PROICM 2018-01 NEX
• Study Type: interventional
• Target: 377
• Locations: 1 country
• Sites: 11

Brief Summary

Patients with metastatic colorectal cancer (mCRC) who have received all approved standard treatments (except Regorafenib and Lonsurf) no longer have treatment options available while maintaining a good performance status which would allow them to receive a new treatment

Conditions

Metastatic Colorectal Cancer (mCRC)

Keywords

REGIRI; regorafenib; irinotecan

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Up to 36 months

Secondary Outcomes (6)

• Progression-free Survival (PFS)

  Up to 36 months

• Time to Deterioration

  Up to 36 months

• Number of Participants With Disease Control Rate

  Through study completion, up to 14 months

• Number of Patients With an Objective Response Rate

  Through treatment completion, up to 14 months

• Assessment of Adverse Events by Using the NCI-CTCAE Version 5.0 Scale (Grade Max Per Patient)

  Up to 36 months

Study Arms (2)

Irinotecan + regorafenib (REGIRI)

EXPERIMENTAL

irinotecan (180 mg/m2) at day1 of each cycle + regorafenib (160 mg/day) from day 2 to day 8

Drug: Regorafenib; Drug: Irinotecan

regorafenib

ACTIVE COMPARATOR

Regorafenib (160 mg/day) for 3 weeks followed by 1 week off

Drug: Regorafenib

Interventions

Regorafenib DRUG

regorafenib tab 40 mg i.e 160 mg/day

Irinotecan + regorafenib (REGIRI); regorafenib

Irinotecan DRUG

irinotecan 120 mg/m2 cycle 1, 150 mg/m2 cycle 2, 180 mg/m2 cycle 3 and more

Irinotecan + regorafenib (REGIRI)

Eligibility Criteria

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

You may qualify if:

• Signed informed consent obtained before any study specific procedures
• Male or female ≥ 18 years of age
• Histological documentation of adenocarcinoma of the colon or rectum
• Patients with metastatic colorectal cancer
• Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti Vascular endothelial growth factor (VEGF) therapy and an anti Epithelial Growth Factor Receptor (EGFR) therapy (for RAS wild-type tumors)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤1
• Life expectancy of at least 3 months
• Patients with A/A cycline D1 (CCND1) genotype of rs603965 CCND1
• International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
• Women of childbearing potential must have a blood or urine pregnancy test performed a maximum of 7 days before start of study treatment, and a negative result must be documented before start of study treatment
• Women of childbearing potential and men must agree to use adequate contraception before entering the study until at least respectively 7 months and 4 months after the last study drug administration of Regorafenib and respectively 6 months and 3 months after the last study drug administration of Irinotecan. The investigator or a designated associate is requested to advise the patient on how to achieve an adequate birth control. Adequate contraception is defined in the study as any medically recommended method (or combination of methods) as per standard of care.

You may not qualify if:

• Patients with A/G or G/G cycline d1 (CCND1) genotype of rs603965 CCND1
• Prior treatment with regorafenib or sorafenib
• Prior treatment with TAS 102
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
• Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug
• Congestive heart failure ≥ New York Heart Association (NYHA) class 2
• 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 \> 140 mmHg or diastolic pressure \> 90 mmHg despite optimal medical management)
• Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea)
• Ongoing infection \> Grade 2 NCI-CTCAE V5.0
• Known history of human immunodeficiency virus (HIV) infection
• Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
• Patients with seizure disorder requiring medication

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (11)

Centre Antoine Lacassagne

Nice, Alpes-Maritimes, 06189, France

Location

Centre François Baclesse

Caen, Basse-Normandie, 14000, France

Location

Hôpital Pontchaillou

Rennes, Ile Et Vilaine, 35000, France

Location

Hôpital Robert Debré

Reims, Marne, 51100, France

Location

Institut Godinot

Reims, Marne, 51100, France

Location

Hôpital Saint-Jean

Perpignan, Pyrénées-orientales, 66000, France

Location

Centre Léon Bérard

Lyon, Rhône, 69008, France

Location

Hôpital privé Jean Mermoz

Lyon, Rhône, 69008, France

Location

Institut Gustave Roussy

Villejuif, Val De Marne, 94800, France

Location

CRLC Val d'Aurelle-Paul Lamarque

Montpellier, 34298, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Related Publications (4)

• Samalin E, Bouche O, Thezenas S, Francois E, Adenis A, Bennouna J, Taieb J, Desseigne F, Seitz JF, Conroy T, Galais MP, Assenat E, Crapez E, Poujol S, Bibeau F, Boissiere F, Laurent-Puig P, Ychou M, Mazard T. Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial. Br J Cancer. 2014 Mar 4;110(5):1148-54. doi: 10.1038/bjc.2013.813. Epub 2014 Jan 9.

  PMID: 24407191 BACKGROUND

• Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res. 2003 Nov 1;63(21):7056-61.

  PMID: 14612495 BACKGROUND

• Alt JR, Cleveland JL, Hannink M, Diehl JA. Phosphorylation-dependent regulation of cyclin D1 nuclear export and cyclin D1-dependent cellular transformation. Genes Dev. 2000 Dec 15;14(24):3102-14. doi: 10.1101/gad.854900.

  PMID: 11124803 BACKGROUND

• Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouche O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. doi: 10.1016/S0140-6736(12)61900-X. Epub 2012 Nov 22.

  PMID: 23177514 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

regorafenib; Irinotecan

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)

Camptothecin; Alkaloids; Heterocyclic Compounds

Limitations and Caveats

* In the protocol, we had planned to randomize 78 patients, but we had also specified that endpoints could be analyzed as soon as 55 events (deaths) were reached (i.e when one of the two is reached first). When inclusion ended, we continued to record deaths and obtained 59 events for 66 randomized patients i.e 33 patients randomized in each arm. * There is no data on race or ethnicity.

Results Point of Contact

• Title: Dr Emmanuelle Samalin
• Organization: Institut régional du Cancer de Montpellier

emmanuelle.samalin@icm.unicancer.fr

467613136

Study Officials

• Emmanuelle SAMALIN, MD

  Institut régional du cancer de Montpellier

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: February 4, 2019
• Study Start: March 28, 2019
• Primary Completion: September 4, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: November 21, 2025
• Results First Posted: July 18, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Access to study data upon written detailed request sent to Institute of Montpellier Cancer after publication.
• Access Criteria: The data shared will be limited to that required for independent mandated verification of the published results, the applicant will need authorization from ICM for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (11)