An open-label, randomized, multicenter, phase II trial designed to estimate the activity of CAPTEM combination versus FOLFIRI as second line treatment in patients who have progressed on or after first-line oxaliplatin - containing chemotherapy for advanced, MGMT methylated, RAS mutated colorectal cancer
- Conditions
- colorectal cancerMedDRA version: 17.0Level: HLTClassification code 10008442Term: ChemotherapiesSystem Organ Class: 100000004865MedDRA version: 17.0Level: LLTClassification code 10069759Term: KRAS mutationSystem Organ Class: 100000004867Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-002417-36-IT
- Lead Sponsor
- Fondazione IRCCS Istituto Nazionale dei Tumori
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 82
•Signed Informed Consent Form
•Histologically or cytologically confirmed adenocarcinoma of the colon and/or rectum, with MGMT promoter methylation and RAS mutation.
•Progressive disease on or after a first-line oxaliplatin-containing chemotherapy regimen for mCRC with or without bevacizumab or other anti-angiogenic drugs. Patients with documented disease relapsed within 6 months from the completion of adjuvant oxaliplatin-based chemotherapy are considered eligible.
•Patients must have received oxaliplatin-containing chemotherapy for = 3 months. No more than one prior chemotherapy regimen for metastatic disease is allowed.
•Disease that is measurable per RECIST v1.1
•Age = 18 years and = 75 years
•Life expectancy = 12 weeks
•ECOG Performance Status of 0 or 1
•Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to first administration of study treatment: ANC = 1500/µL Platelet count = 100,000/µL Hemoglobin = 9.0 g/dL Albumin = 2.5 g/dL
•Total bilirubin = 1.5 × the upper limit of normal (ULN)
•AST, ALT, and/or alkaline phosphatase = 2.5 × ULN, with the following exceptions: Patients with documented hepatic metastases are eligible with AST, ALT, and/or alkaline phosphatase = 5 × ULN. Patients with documented bone metastases are eligible with alkaline phosphatase = 5 × ULN.
•Serum creatinine = 1.5 × ULN, or creatinine clearance = 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation: (140 - age) × (weight in kg) × (0.85 if female) 72 × (serum creatinine in mg/dL)
•INR and aPTT = 1.5 × ULN
•For female patients of childbearing potential and male patients with partners of childbearing potential, documented agreement (by patient and/or partner) to use an effective means of contraception (e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants) and to continue its use for the duration of the study and for 60 days for female patients or 150 days for male patients with partners of childbearing potential after the last infusion of study treatment.
•Consent to provide mandatory archival tumor tissue for biomarker testing
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 41
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41
•Prior treatment with irinotecan and temozolomide
•Major surgical procedure within 4 weeks and radiotherapy within 2 weeks prior to Day 1 Cycle 1
•Symptomatic hypercalcemia requiring continued use of bisphosphonate therapy. Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
•Known clinically significant dihydropyrimidine dehydrogenase deficiency
•Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders; ulcers or bone fractures), active infection requiring IV antibiotics
•History of heart failure of any New York Heart Association criteria or serious cardiac arrhythmia requiring treatment (except for atrial fibrillation and paroxysmal supraventricular tachycardia)
•History of myocardial infarction within 6 months prior to Cycle 1, Day 1, or history of unstable angina
•Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; or current alcohol abuse
•History of bleeding diathesis or coagulopathy other than that due to anticoagulation therapy
•Patients receiving oral coumarin-derived anticoagulants
•Active haemoptysis (defined as bright red blood of ½ teaspoon or more) within 30 days prior to Cycle 1, Day 1
•Known HIV infection
•Untreated/active CNS metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible provided they meet all of the following criteria:
Measurable disease outside the CNS as defined by RECIST v1.1.Radiotherapy completed = 4 weeks prior to Cycle, 1 Day 1
•Pregnancy (positive pregnancy test) or lactation. Women of childbearing potential (including those who have had a tubal ligation) must have a documented negative serum pregnancy test within 14 days prior to Cycle 1, Day 1.
•Inability to take oral medications.
•Malignancies other than CRC within 3 years prior to randomization, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Progression free survival;Secondary Objective: Overall survival;Primary end point(s): • To evaluate the efficacy, measured by progression-free survival, of FOLFIRI (administered every 2 weeks) versus CAPTEM (administered four-weekly) ;Timepoint(s) of evaluation of this end point: every 8 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): To evaluate the activity of the two regimens, as measured by response rate; secondary efficacy endpoints also include duration of response and overall survival of FOLFIRI (administered every 2 weeks) versus CAPTEM (administered four-weekly) <br>• To evaluate the safety and tolerability of FOLFIRI versus CAPTEM<br>• To assess the quality of life as measured by EORTC QLQ – CR29 QLQ-C30 <br>;Timepoint(s) of evaluation of this end point: every 8 weeks