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

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT00752570

Collaborator

(none)

144

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer Carcinoma Colon Cancer Colorectal Cancer Gastrointestinal Cancer Metastases Metastatic Cancer Metastatic Colorectal Cancer Oncology Rectal Cancer	Drug: AMG 386 Drug: AMG 386 Placebo Drug: FOLFIRI	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

144 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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 Start Date :

Nov 1, 2008

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

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

Arm

Intervention/Treatment

Placebo Comparator: 2

AMG 386 placebo QW, FOLFIRI Q2W

Drug: AMG 386 Placebo

AMG 386 placebo QW will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.

Drug: FOLFIRI

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.

Active Comparator: 1

Arm 1 : AMG 386 10 mg/kg QW, FOLFIRI Q2W

Drug: AMG 386

AMG 386 (10 mg/kg QW) will be administered until subject develops disease progression, clinical progression, unacceptable toxicity, or withdraws consent.

Drug: FOLFIRI

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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])