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

Study Overview
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Brief Summary
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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.

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

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

Intervention / Treatment
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* Drug: AMG 386
* Drug: AMG 386 Placebo
* Drug: FOLFIRI


Participation Criteria
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Eligibility Criteria
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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])

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 2<br>AMG 386 placebo QW, FOLFIRI Q2W | Drug: AMG 386 Placebo<br>* AMG 386 placebo QW will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.<br>Drug: FOLFIRI<br>* 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.<br>|
| Active Comparator: 1<br>Arm 1 : AMG 386 10 mg/kg QW, FOLFIRI Q2W | Drug: AMG 386<br>* AMG 386 (10 mg/kg QW) will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.<br>Drug: FOLFIRI<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 progression free survival and measures of efficacy by KRAS status |  | 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) |  | Throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic Colorectal Cancer, colorectal cancer, colon cancer