Study to Compare CAPTEM vs FOLFIRI as Second Line Treatment in Advanced, Colorectal Cancer Patients

Sponsor
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Study ID
NCT02414009
Phase
PHASE2
Status
Completed

Conditions

  • Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Capecitabine — DRUG
    Patients in Arm A will receive capecitabine at the oral dose of 1500 mg/mq/die refracted in two daily doses from day 1 to day 14 every 28 days
  • Temozolomide — DRUG
    Patients in Arm A will receive temozolomide 150 mg/mq/die refracted in two daily doses starting on day 10 to 14 every 28 days.
  • Irinotecan — DRUG
    Patients in Arm B will receive FOLFIRI chemotherapy starting Day 1 q2w (every cycle) starting on Day 1 of Cycle 1. FOLFIRI consists of irinotecan (starting dose of 180 mg/m2) on day one only; 5-FU (starting bolus and 22-hour infusional doses of 400 mg/m2 and 600 mg/m2, respectively), and leucovorin (racemic, starting dose of 200 mg/m2 or L-form, starting dose of 100 mg/m2) for two consecutive days.
  • Fluorouracil — DRUG
    Patients in Arm B will receive FOLFIRI chemotherapy starting Day 1 q2w (every cycle) starting on Day 1 of Cycle 1. FOLFIRI consists of irinotecan (starting dose of 180 mg/m2) on day one only; 5-FU (starting bolus and 22-hour infusional doses of 400 mg/m2 and 600 mg/m2, respectively), and leucovorin (racemic, starting dose of 200 mg/m2 or L-form, starting dose of 100 mg/m2) for two consecutive days.
  • Leucovorin — DRUG
    Patients in Arm B will receive FOLFIRI chemotherapy starting Day 1 q2w (every cycle) starting on Day 1 of Cycle 1. FOLFIRI consists of irinotecan (starting dose of 180 mg/m2) on day one only; 5-FU (starting bolus and 22-hour infusional doses of 400 mg/m2 and 600 mg/m2, respectively), and leucovorin (racemic, starting dose of 200 mg/m2 or L-form, starting dose of 100 mg/m2) for two consecutive days.

Study Details

Open-label, randomized, multicenter, Phase II trial designed to estimate the efficacy of CAPTEM versus FOLFIRI as second line treatment in MGMT methylated, RAS mutated advanced CRC patients who have progressed on or after first-line oxaliplatin containing chemotherapy for metastatic disease. MGMT will be assessed centrally at Pathology Department of Fondazione IRCCS Istituto Nazionale dei Tumori prior to enrollment. A minimum of ten 3-micron unstained sections on charged slides of tumor will be required and methylation status will be provided within a maximum of seven days to the Study Centers. Presence of RAS mutation will be assessed at each local participating center. Eligible patients will be randomized in a 1:1 ratio to one of two treatment arms: * Arm A (experimental arm): CAPTEM * Arm B (control arm): FOLFIRI Study treatment will be given in cycles repeated every 28 days for Arm A and every 14 days for Arm B. Patients in Arm A will receive capecitabine at the oral dose of 1500 mg/mq/die bid from day 1 to day 14 every 28 days plus temozolomide 150 mg/mq/die bid starting on day 9 to 14 every 28 days. Patients in Arm B will receive FOLFIRI chemotherapy starting Day 1 q2w (every cycle) starting on Day 1 of Cycle 1. FOLFIRI consists of irinotecan (starting dose of 180 mg/m2) on day one only; 5-FU 7 (starting bolus and 22-hour infusional doses of 400 mg/m2 and 600 mg/m2, respectively), and leucovorin (racemic, starting dose of 200 mg/m2 or L-form, starting dose of 100 mg/m2) for two consecutive days. Treatment will continue for up to 6 cycles in Arm A and up to 12 cycles in Arm B or up to disease progression, unacceptable toxicity or informed consent withdrawal. Randomization will be stratified across the treatment arms by the following predefined stratification variables: disease progression within 9 months from the start of first-line oxaliplatin-containing chemotherapy (\< vs. ≥9 months); prior bevacizumab in combination with oxaliplatin-based chemotherapy (yes vs. no). Efficacy assessments will be performed every 2 cycles in Arm A and every 4 cycles in Arm B until progression. The study is expected to enrol approximately 82 patients who meet the eligibility criteria.

Key Dates

Start date
Sep 30, 2014
Status verified
Sep 2021
Primary completion
Jul 30, 2019
Completion
Jul 30, 2019

Study Design

Enrollment
82 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: CAPTEM
    Patients in Arm A will receive capecitabine at the oral dose of 1500 mg/mq/die bid from day 1 to day 14 every 28 days plus temozolomide 150 mg/mq/die bid starting on day 10 to 14 every 28 days. Treatment will continue for up to 6 cycles or up to disease progression, unacceptable toxicity or informed consent withdrawal.
  • Active Comparator: FOLFIRI
    Patients in Arm B will receive FOLFIRI chemotherapy starting Day 1 q2w (every cycle) starting on Day 1 of Cycle 1. FOLFIRI consists of irinotecan (starting dose of 180 mg/m2) on day one only; 5-FU 7 (starting bolus and 22-hour infusional doses of 400 mg/m2 and 600 mg/m2, respectively), and leucovorin (racemic, starting dose of 200 mg/m2 or L-form, starting dose of 100 mg/m2) for two consecutive days. Treatment will continue for up to 12 cycles in Arm B or up to disease progression, unacceptable toxicity or informed consent withdrawal.

Primary Outcome Measure

Progression-free survival of FOLFIRI versus CAPTEM [ Time Frame: 30 months ]

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