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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00752570
• Other study ID #: 20070307
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2008
• Last updated: August 14, 2015
• Start date: November 2008
• Est. completion date: June 2012

Study information

• Verified date: August 2015
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines AgencyUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 144
• Est. completion date: June 2012
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

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])

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Carcinoma
• Colon Cancer
• Colorectal Cancer
• Colorectal Neoplasms
• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• Metastases
• Metastatic Cancer
• Metastatic Colorectal Cancer
• Neoplasm Metastasis
• Oncology
• Rectal Cancer

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Yes
Secondary	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	Yes
Secondary	To evaluate progression free survival and measures of efficacy by KRAS status		Treatment phase	No
Secondary	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	Yes

External Links

•   AmgenTrials clinical trials website