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

August 14, 2015 updated by: Amgen
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

144

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / 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: 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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.
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).
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
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
Time Frame: Treatment phase or until disease progression
Treatment phase or until disease progression
To evaluate progression free survival and measures of efficacy by KRAS status
Time Frame: Treatment phase
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)
Time Frame: Throughout study
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Actual)

September 1, 2010

Study Completion (Actual)

June 1, 2012

Study Registration Dates

First Submitted

September 11, 2008

First Submitted That Met QC Criteria

September 12, 2008

First Posted (Estimate)

September 15, 2008

Study Record Updates

Last Update Posted (Estimate)

September 2, 2015

Last Update Submitted That Met QC Criteria

August 14, 2015

Last Verified

August 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20070307

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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