Phase 1b/2 Study of AMG 655 With mFOLFOX6 and Bevacizumab for First-Line Metastatic Colorectal Cancer

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT00625651

Collaborator

(none)

202

Enrollment

Locations

Arms

Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This phase 1/2, multi-center, randomized, double-blind, placebo-controlled trial is designed to evaluate the efficacy and safety of AMG 655 when combined with mFOLFOX6 and bevacizumab compared with mFOLFOX6 and bevacizumab alone in subjects with previously untreated metastatic colorectal cancer (CRC).

The clinical benefit of AMG 655 in combination with mFOLFOX6 and bevacizumab will be measured by progression-free survival, objective response rate, time to response, duration of response, and overall survival. This study is also designed to evaluate the safety and tolerability of AMG 655 in combination with mFOLFOX6 and bevacizumab and to evaluate anti-AMG 655 antibody formation and the pharmacokinetics of AMG 655.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Colorectal Cancer Colon Cancer Colorectal Cancer Rectal Cancer	Drug: Placebo Drug: AMG 655 Drug: Modified FOLFOX6 Drug: Bevacizumab	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

202 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2 Study of AMG 655 in Combination With Modified FOLFOX6 and Bevacizumab for the First-Line Treatment of Subjects With Metastatic Colorectal Cancer

Study Start Date :

Oct 1, 2007

Actual Primary Completion Date :

Aug 1, 2010

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AMG 655 Low Dose AMG 655 (low dose) + mFOLFOX6 + Bevacizumab	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5). Drug: Modified FOLFOX6 Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days) Other Names: mFOLFOX6 Drug: Bevacizumab Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).
Placebo Comparator: Placebo Placebo + mFOLFOX6 + Bevacizumab	Drug: Placebo Inactive dummy AMG 655 (to maintain blind) Drug: Modified FOLFOX6 Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days) Other Names: mFOLFOX6 Drug: Bevacizumab Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).
Experimental: AMG 655 High Dose AMG 655 (high dose) + mFOLFOX6 + Bevacizumab	Drug: AMG 655 AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5). Drug: Modified FOLFOX6 Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days) Other Names: mFOLFOX6 Drug: Bevacizumab Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).

Arm

Intervention/Treatment

Experimental: AMG 655 Low Dose

AMG 655 (low dose) + mFOLFOX6 + Bevacizumab

Drug: AMG 655

AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).

Drug: Modified FOLFOX6

Combination treatment comprising oxaliplatin (85 mg/m2), leucovorin (400 mg/m2) and bolus 5-FU (400 mg/m2) and continuous IV 5-FU (2400 mg/m2)] administered by intravenous infusion once every 14 days (+3 days)

Other Names:

mFOLFOX6

Drug: Bevacizumab

Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).

Placebo Comparator: Placebo

Placebo + mFOLFOX6 + Bevacizumab

Drug: Placebo

Inactive dummy AMG 655 (to maintain blind)

Drug: Modified FOLFOX6

Other Names:

mFOLFOX6

Drug: Bevacizumab

Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).

Experimental: AMG 655 High Dose

AMG 655 (high dose) + mFOLFOX6 + Bevacizumab

Drug: AMG 655

AMG 655 is an investigational, fully human monoclonal agonist antibody that selectively binds to Death Receptor-5 (DR5).

Drug: Modified FOLFOX6

Other Names:

mFOLFOX6

Drug: Bevacizumab

Bevacizumab will be administered at a dose of 5 mg/kg by intravenous infusion on day 1 of each 14 day cycle (+3 days).

Outcome Measures

Primary Outcome Measures

Progression-free survival [Length of study]

Secondary Outcome Measures

Objective response rate [Length of study]
Duration of response [Length of study]
Time-to-response [Length of study]
Overall survival [Length of study]
AMG 655 pharmacokinetic parameters [Length of study]
The incidence of anti-AMG 655 antibody formation [Length of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum.
Subjects with measurable or unmeasurable disease
Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
Men or women at least 18 years of age
Adequate hematologic, renal, hepatic and coagulation function

Exclusion Criteria:

History or known presence of central nervous system (CNS) metastases
Prior chemotherapy or other systemic therapy for advanced or metastatic CRC
Any investigational agent or therapy for advanced or metastatic CRC
Clinically significant cardiac disease
Clinically significant peripheral neuropathy
Active inflammatory bowel disease
Recent gastrointestinal ulcer or hemorrhage
Recent arterial thrombotic event or pulmonary embolus
Recent history of clinically significant bleeding, bleeding diathesis, or coagulopathy
Recent major surgical procedure or not yet recovered from major surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Hot Springs	Arkansas	United States	71913
2	Research Site	Downey	California	United States	90241
3	Research Site	La Jolla	California	United States	92093-0957
4	Research Site	Loma Linda	California	United States	92354
5	Research Site	Orange	California	United States	92868
6	Research Site	Rancho Mirage	California	United States	92270
7	Research Site	San Diego	California	United States	92123
8	Research Site	Denver	Colorado	United States	80218
9	Research Site	Newark	Delaware	United States	19718
10	Research Site	Washington	District of Columbia	United States	20007
11	Research Site	Boca Raton	Florida	United States	33486
12	Research Site	Kissimmee	Florida	United States	34741
13	Research Site	Leesburg	Florida	United States	34788
14	Research Site	Miami	Florida	United States	33136
15	Research Site	Miami	Florida	United States	33176
16	Research Site	Atlanta	Georgia	United States	30309
17	Research Site	Lawrenceville	Georgia	United States	30045
18	Research Site	Harvey	Illinois	United States	60426
19	Research Site	Maywood	Illinois	United States	60153
20	Research Site	Indianapolis	Indiana	United States	46227
21	Research Site	Overland Park	Kansas	United States	66210
22	Research Site	Louisville	Kentucky	United States	40202
23	Research Site	Baltimore	Maryland	United States	21215
24	Research Site	Baltimore	Maryland	United States	21237
25	Research Site	Boston	Massachusetts	United States	02115
26	Research Site	Ann Arbor	Michigan	United States	48106-0995
27	Research Site	St. Joseph	Michigan	United States	49085
28	Research Site	Rochester	Minnesota	United States	55905
29	Research Site	St. Louis	Missouri	United States	63136
30	Research Site	Great Falls	Montana	United States	59405
31	Research Site	Long Branch	New Jersey	United States	07740
32	Research Site	Albuquerque	New Mexico	United States	87109-4397
33	Research Site	Bronx	New York	United States	10469
34	Research Site	Buffalo	New York	United States	14263
35	Research Site	Hudson	New York	United States	12534
36	Research Site	New York	New York	United States	10021
37	Research Site	Asheville	North Carolina	United States	28801
38	Research Site	Burlington	North Carolina	United States	27215
39	Research Site	Gastonia	North Carolina	United States	28054
40	Research Site	Raleigh	North Carolina	United States	27607
41	Research Site	Winston Salem	North Carolina	United States	27103
42	Research Site	Cincinnati	Ohio	United States	45226
43	Research Site	Columbus	Ohio	United States	43219
44	Research Site	Middletown	Ohio	United States	45042
45	Research Site	Portland	Oregon	United States	97227
46	Research Site	Harrisburg	Pennsylvania	United States	17109
47	Research Site	Philadelphia	Pennsylvania	United States	19107
48	Research Site	Pottsville	Pennsylvania	United States	17901
49	Research Site	Greenville	South Carolina	United States	29605
50	Research Site	Memphis	Tennessee	United States	38120
51	Research Site	Nashville	Tennessee	United States	37203
52	Research Site	Austin	Texas	United States	78731
53	Research Site	Richardson	Texas	United States	75080
54	Research Site	Tyler	Texas	United States	75702
55	Research Site	Wichita Falls	Texas	United States	76310
56	Research Site	Ogden	Utah	United States	84403
57	Research Site	Fairfax	Virginia	United States	22031
58	Research Site	Norfolk	Virginia	United States	23502
59	Research Site	Richmond	Virginia	United States	23235
60	Research Site	Tacoma	Washington	United States	98405
61	Research Site	Vancouver	Washington	United States	98684