A Phase 2, Randomized, Double Blind, Placebo Controlled Study of AMG 386 in Combination With FOLFIRI in Subjects With Previously Treated Metastatic Colorectal Carcinoma

Phase 2

Completed

Conditions: Cancer
Colorectal Cancer
Oncology
Carcinoma
Colon Cancer
Gastrointestinal Cancer
Metastases
Metastatic Cancer
Metastatic Colorectal Cancer
Rectal Cancer

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

Histologically confirmed adenocarcinoma of the colon or rectum in patients who are presenting with metastatic disease
One and only one prior chemotherapy regimen for metastatic disease consisting of the combination of a fluoropyrimidine-based chemotherapy and an oxaliplatin-based chemotherapy. Prior adjuvant chemotherapy used prior to the onset of metastatic disease is permitted
At least one uni dimensionally measurable lesion per modified RECIST criteria. All sites of disease must be evaluated <= 28 days before randomization
Radiographically documented disease progression per modified RECIST criteria either while receiving or <= 6 months after the last dose of prior chemotherapy regimen for metastatic disease
ECOG performance status of 0 or 1
Man or woman >= 18 years of age
Adequate end organ assessments by laboratory studies (hematological and chemistries)
Life expectancy >= 3 months

Exclusion Criteria

Exclude subjects with a history of prior malignancy, except:
- Malignancy treated with curative intent and with no known active disease present for >= 3 years before enrollment and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
Prior irinotecan therapy
Systemic chemotherapy, hormonal therapy, or immunotherapy <= 21 days prior to randomization
Experimental or approved proteins/antibodies (eg, bevacizumab) <= 30 days prior to randomization
Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
Known allergy or hypersensitivity to irinotecan, 5 FU (known dihydropyrimidine dehydrogenase deficiency) or leucovorin
Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as >= CTC grade 2 [CTCAE version 3.0])

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
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.	The time frame will be event driven and will occur when 100 subjects have experienced a PFS event (radiographic disease progression or death).

Secondary Outcome Measures

Name	Time	Method
To evaluate progression free survival and measures of efficacy by KRAS status	Treatment phase
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	Treatment phase or until disease progression
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)	Throughout study