This clinical trial will compare the efficacy and safety of the combination of AMG 386 and FOLFIRI with FOLFIRI alone in second line treatment of metastatic colorectal cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
144
AMG 386 (10 mg/kg QW) will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.
AMG 386 placebo QW will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.
Administration of FOLFIRI chemotherapy will commence on day 1 of each dosing week following the administration of AMG 386. FOLFIRI Q2W regimen: irinotecan 180 mg/m2 IV over 90 (+-15) minutes on Day 1, leucovorin 400 mg/m2 IV over 2 hrs on Day 1, 5 FU 400mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hrs +- 2 hours. FOLFIRI will be administered until disease progression, FOLFIRI intolerability, death, or study withdrawal by the subject, investigator, or sponsor, whichever occurs earliest.
To estimate the treatment effect as measured by progression free survival (PFS) in subjects treated with AMG 386 + FOLFIRI relative to subjects treated with FOLFIRI + placebo.
Time frame: The time frame will be event driven and will occur when 100 subjects have experienced a PFS event (radiographic disease progression or death).
To evaluate other measures of efficacy or clinical response including objective response rate (ORR), duration of response (DOR), overall survival (OS) in subjects treated with AMG 386 + FOLFIRI relative to subjects treated with FOLFIRI + placebo
Time frame: Treatment phase or until disease progression
To evaluate progression free survival and measures of efficacy by KRAS status
Time frame: Treatment phase
To evaluate patient reported outcomes (PROs), relative dose intensity, incidence of anti AMG 386 antibody formation, pharmacokinetics of AMG 386 (Cmax and AUC) and safety (incidence of AEs and significant laboratory changes)
Time frame: Throughout study
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