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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00752570
First received: September 11, 2008
Last updated: January 10, 2013
Last verified: January 2013
  Purpose

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 Intervention 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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Amgen:

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. [ 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). ] [ Designated as safety issue: Yes ]

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 [ Time Frame: Treatment phase or until disease progression ] [ Designated as safety issue: Yes ]
  • To evaluate progression free survival and measures of efficacy by KRAS status [ Time Frame: Treatment phase ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 144
Study Start Date: November 2008
Study Completion Date: June 2012
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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])
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00752570

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided by Amgen

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00752570     History of Changes
Other Study ID Numbers: 20070307
Study First Received: September 11, 2008
Last Updated: January 10, 2013
Health Authority: European Union: European Medicines Agency
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Amgen:
Metastatic Colorectal Cancer
colorectal cancer
colon cancer

Additional relevant MeSH terms:
Carcinoma
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Gastrointestinal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on July 23, 2014