Sequences Of REGorafenib And Trifluridine/Tipiracil in Patients With Metastatic Colorectal Cancer

NCT04450836 | Terminated Phase 2 DMC

• 3 other identifiers: UC-GIG-19102019-004196-39PRODIGE 68 - UCGI 38
• Study Type: interventional
• Target: 234
• Locations: 2 countries
• Sites: 36

Brief Summary

A randomized, phase II study comparing the sequences of regorafenib and trifluridine/tipiracil, after failure of standard therapies in patients with metastatic colorectal cancer

Conditions

Metastatic Colorectal Cancer

Keywords

Regorafenib; Trifluridine/Tipiracil; Metastatic colorectal cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the feasibility of treatment sequence (R-TT or TT-R)

  The feasibility of the treatment sequence is defined as the percentage of subjects able to receive both regorafenib and trifluridine/tipiracil according to the sequence in 3rd and 4th line. Subjects will be considered as having received both 3rd and 4th lines if they are administered at least two cycles of each line of therapy, i.e. percentage of patients being treated until the first tumor evaluation.

  Expected duration of 5 months from randomization

Secondary Outcomes (10)

• To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of Overall Survival rate

  Expected duration of 9 months from randomization

• To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the progression-free Survival 1 (PFS1)

  Expected duration of 3 months from randomization

• To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Progression-free survival 2 (PFS2)

  Expected duration of 6 months from randomization

• To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Disease control rate (DCR)

  Expected duration of 6 months from randomization

• To evaluate the efficacy of treatment sequence (R-TT or TT-R) in terms of the Objective response rate (ORR)

  Expected duration of 6 months from randomization

Study Arms (2)

Arm A (R-TT)

EXPERIMENTAL

Regorafenib followed by trifluridine-tipiracil.

Drug: Regorafenib then Trifluridine/Tipiracil

Arm B (TT-R)

EXPERIMENTAL

Trifluridine-tipiracil followed by Regorafenib.

Drug: Trifluridine/Tipiracil then Regorafenib

Interventions

Regorafenib then Trifluridine/Tipiracil DRUG

REGORAFENIB 160 mg per day during 3 weeks followed by 1 week off of each 4-week cycle except for cycle 1. During first cycle: dose is started at 80 mg per day at week 1, 120 mg per day at week 2, 160 mg per day at week 3, followed by 1 week off. Then TRIFLURIDINE/TIPIRACIL 35 mg/m² Dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 4-week cycle.

Also known as: STIVARGA, LONSURF

Arm A (R-TT)

Trifluridine/Tipiracil then Regorafenib DRUG

TRIFLURIDINE/TIPIRACIL 35 mg/m² Dose administered orally twice daily on Days 1 to 5 and Days 8 to 12 of each 4-week cycle. Then REGORAFENIB 160 mg per day during 3 weeks followed by 1 week off of each 4-week cycle except for cycle 1. During first cycle: dose is started at 80 mg per day at week 1, 120 mg per day at week 2, 160 mg per day at week 3, followed by 1 week off.

Also known as: LONSURF, STIVARGA

Arm B (TT-R)

Eligibility Criteria

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

You may qualify if:

• Patients must have provided informed consent before performing any study specific procedures.
• Histological or cytological documented adenocarcinoma of the colon or rectum.
• Patients with metastatic colorectal cancer (stage IV).
• Measurable disease, defined as at least one unidimensional measurable lesion on a computed tomography (CT) scan according to RECIST v1.1.
• The patient must have progressed following exposure of all the following agents : one fluoropyrimidine-based chemotherapy (capecitabine or fluorouracil \[5-FU\], combined with oxaliplatin and/or irinotecan (including FOLFOX, FOLFIRI or FOLFOXIRI) as well as EGFR and/or VEGF inhibitors in patients eligible for these treatments.
• Patients considered eligible for treatment with both regorafenib and trifluridine-tipiracil.
• Male or female patients aged ≥18 years.
• ECOG performance status of ≤1.
• Adequate bone marrow, liver and renal functions as assessed by the following laboratory requirements:
• Total bilirubin ≤1.5 x upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN (≤5 x ULN for patients with liver metastasis).
• Alkaline phosphatase limit ≤2.5 x ULN (≤5 x ULN for patients with liver metastasis).
• Serum creatinine ≤1.5 x ULN.
• International normalized ratio (INR) and partial thromboplastin time (PTT) ≤1.5 x ULN. Patients receiving anticoagulants, such as warfarin or heparin are eligible if there is no prior evidence of an underlying abnormality with coagulation.
• Women of childbearing potential and men must agree to use a highly effective contraception (1% failure rate) from the signing of the informed consent form until at least 6 months after the last study drug administration. Women using hormonal contraceptive must also use a barrier method.

You may not qualify if:

• Patients with symptomatic brain or meningeal metastasis, unless definitive therapy occurred more than 6 months ago and with a confirmation of tumoral control within 4 weeks of starting study treatment.
• Prior treatment with regorafenib or any other tyrosine kinase inhibitor.
• Prior treatment with trifluridine/tipiracil.
• Known hypersensitivity to any of the study drugs, study drug classes, or study drug excipients.
• Unresolved toxicity grade \>1 (by CTCAE v5.0) caused by prior therapy/procedure, excluding alopecia, hypothyroidism, and oxaliplatin-induced neurotoxicity grade ≤2.
• Patient with moderate or severe hepatic impairment (Child-Pugh C).
• Known UGT1A1 polymorphisms. History of Gilbert's syndrome.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before starting study treatment.
• Chemotherapy within 21 days of starting study treatment.
• Radiotherapy within 4 weeks of starting study treatment, except for palliative radiotherapy within 2 weeks.
• Active cardiac disease including any of the Following:
• Congestive heart Failure: New York Heart Association (NYHA) class ≥2.
• Unstable angina (angina symptoms at rest), or a new-onset angina (within the 3 months before enrolment).
• Myocardial infarction that occurred less than 6 months before enrolment.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (treatment with beta blockers or digoxin are permitted)

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (36)

Clinique Saint Luc

Bouge, 5004, Belgium

Location

CH de l'Ardenne

Libramont, 6800, Belgium

Location

CH Verviers

Verviers, 4800, Belgium

Location

Hôpital Privé Pays de Savoie

Annemasse, France

Location

Centre hospitalier d'Auxerre

Auxerre, France

Location

Institut Sainte Catherine

Avignon, 84000, France

Location

Centre Hospitalier de Bayeux

Bayeux, France

Location

Centre François Baclesse

Caen, France

Location

Infirmerie Protestante de Lyon

Caluire-et-Cuire, 69300, France

Location

CH Cotentin

Cherbourg, 50102, France

Location

Institut de Cancérologie de Bourgogne

Dijon, 21000, France

Location

Centre Oscar Lambret

Lille, France

Location

Hôpital Scorff

Lorient, 56322, France

Location

Centre Léon Bérard

Lyon, France

Location

Association Hôpital Saint Joseph de Marseille

Marseille, 13008, France

Location

Hôpital privé du Confluent

Nantes, 44277, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital Privé des Peupliers

Paris, 75013, France

Location

APHP - Hôpital Européen Georges Pompidou

Paris, France

Location

Groupe hospitalier Pitié Salpétrière

Paris, France

Location

CH Saint Jean

Perpignan, France

Location

CHU de Bordeaux - Hôpital Haut Lévèque

Pessac, France

Location

CH Périgueux

Périgueux, 24000, France

Location

Hôpital Privé des Côtes d'Armor - Centre CARIO-HPCA

Plérin, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU - Robert Debre

Reims, 51092, France

Location

Institut Jean Godinot

Reims, France

Location

Hopital Charles Nicolle

Rouen, France

Location

CHU Hôpital Nord

Saint-Etienne, 42270, France

Location

Centre Hospitalier de Saint Malo

St-Malo, France

Location

Centre Paul Strauss (ICANS)

Strasbourg, France

Location

CHU de Toulouse

Toulouse, 31059, France

Location

Centre Hospitalier de Valence

Valence, 26000, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

Paul Brousse

Villejuif, 94800, France

Location

Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

tipiracil; regorafenib; trifluridine tipiracil drug combination; Trifluridine

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)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Michel MD DUCREUX, Pr

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

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: June 24, 2020
• First Posted: June 30, 2020
• Study Start: November 23, 2020
• Primary Completion: March 23, 2024
• Study Completion: December 31, 2024
• Last Updated: March 30, 2025

Record last verified: 2025-03

Locations

FR (33); BE (3)