Status:
TERMINATED
Sequences Of REGorafenib And Trifluridine/Tipiracil in Patients With Metastatic Colorectal Cancer
Lead Sponsor:
UNICANCER
Conditions:
Metastatic Colorectal Cancer
Eligibility:
All Genders
18+ years
Phase:
PHASE2
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
Detailed Description
Multicenter, international, comparative, randomized, open-label, phase II study conducted in two parallel groups. The study population will consist of male and female patients aged ≥18 years old with...
Eligibility Criteria
Inclusion
- 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.
- Platelet count ≥75000 /mm³, hemoglobin (Hb) ≥9 g/dL, absolute neutrophil count (ANC) ≥1500/mm³. Blood transfusions to meet this inclusion criterion are not allowed.
- 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.
- Women of childbearing potential must have a negative pregnancy test within 7 days before starting study treatment.
- Patients affiliated to the social security system.
- Patient willing and able to comply with the protocol for the duration of the study including treatment, scheduled visits, and examinations throughout the study, including follow up.
Exclusion
- 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.
- Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated in situ cervical cancer, non-melanoma skin cancer, and superficial bladder tumors: staged Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor with lamina propria invasion).
- 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)
- Uncontrolled hypertension (systolic blood pressure \>140 mmHg or diastolic pressure \>90 mmHg despite treatment).
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 6 months of starting study treatment.
- Ongoing infection grade 2 (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.
- Patients with a history of any bleeding diathesis, irrespective of the severity.
- Any hemorrhage or bleeding event grade ≥3 (CTCAE v5.0) within 4 weeks before starting study treatment.
- Presence of a wound, ulcer, or bone fracture that is not healing.
- Patients unable to swallow oral medications.
- Bowel malabsorption or extended bowel resection that could affect the absorption of regorafenib, occlusive syndrome.
- Presence of gastro-intestinal fistula or perforation.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and their compliance in the study.
- Patients participating in another therapeutic study within the 30 days before enrolment.
- Pregnant or breast feeding women.
- Person deprived of their liberty or under protective custody or guardianship.
Key Trial Info
Start Date :
November 23 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 31 2024
Estimated Enrollment :
234 Patients enrolled
Trial Details
Trial ID
NCT04450836
Start Date
November 23 2020
End Date
December 31 2024
Last Update
March 30 2025
Active Locations (36)
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1
Clinique Saint Luc
Bouge, Belgium, 5004
2
CH de l'Ardenne
Libramont, Belgium, 6800
3
CH Verviers
Verviers, Belgium, 4800
4
Hôpital Privé Pays de Savoie
Annemasse, France