Ph II Trial of a Novel Anti-angiogenic Agent in Combination With Chemotherapy for the Second-line Treatment of Metastatic Colorectal Cancer

Sponsor

Bristol-Myers Squibb (Industry)

Overall Status

Completed

CT.gov ID

NCT00851045

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

1.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy of CT-322 comparative to bevacizumab, both in combination with irinotecan, 5-FU and leucovorin in the second-line treatment of subject with metastatic colorectal cancer

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer (CRC)	Drug: Irinotecan Drug: 5-Fluorouracil (bolus) Drug: 5-Fluorouracil (infusional) Drug: Leucovorin calcium Drug: CT-322 Drug: Bevacizumab Drug: Bevacizumab Placebo (saline solution)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Phase II Trial of CT-322 (BMS-844203) Plus Irinotecan, 5-FU and Leucovorin (FOLFIRI) Versus Bevacizumab Plus FOLFIRI as Second-Line Treatment for Metastatic Colorectal Cancer

Study Start Date :

Oct 1, 2009

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 Irinotecan/5-Fluorouracil (bolus)/5-Fluorouracil (infusional)/Leucovorin calcium/CT-322	Drug: Irinotecan Solution, IV, 180 mg/m2, Q14 days, Until PD Other Names: Camptosar Drug: 5-Fluorouracil (bolus) Solution, IV, 400 mg/m2, Q14 days, Until PD Drug: 5-Fluorouracil (infusional) Solution, IV, 2400 mg/m2, Q14 days, Until PD Drug: Leucovorin calcium Solution, IV, 400 mg/m2, Q14 days, Until PD Drug: CT-322 Solution, IV, 2 mg/kg, Q7 days, Until PD Other Names: BMS-844203
Active Comparator: Arm 2 Irinotecan/5-Fluorouracil(bolus)/5-Fluorouracil(infusional)/Leucovorin calcium /Bevacizumab/Bevacizumab Placebo(saline solution)	Drug: Irinotecan Solution, IV, 180 mg/m2, Q14 days, Until PD Other Names: Camptosar Drug: 5-Fluorouracil (bolus) Solution, IV, 400 mg/m2, Q14 days, Until PD Drug: 5-Fluorouracil (infusional) Solution, IV, 2400 mg/m2, Q14 days, Until PD Drug: Leucovorin calcium Solution, IV, 400 mg/m2, Q14 days, Until PD Drug: Bevacizumab Solutions, IV, 5 mg/kg, Q14 days, Until PD Other Names: Avastin Drug: Bevacizumab Placebo (saline solution) Solution, IV, 0 mg/kg, On day 8 of a 2-week cycle, Until PD Other Names: Saline Solution

Arm

Intervention/Treatment

Active Comparator: Arm 1

Irinotecan/5-Fluorouracil (bolus)/5-Fluorouracil (infusional)/Leucovorin calcium/CT-322

Drug: Irinotecan

Solution, IV, 180 mg/m2, Q14 days, Until PD

Other Names:

Camptosar

Drug: 5-Fluorouracil (bolus)

Solution, IV, 400 mg/m2, Q14 days, Until PD

Drug: 5-Fluorouracil (infusional)

Solution, IV, 2400 mg/m2, Q14 days, Until PD

Drug: Leucovorin calcium

Solution, IV, 400 mg/m2, Q14 days, Until PD

Drug: CT-322

Solution, IV, 2 mg/kg, Q7 days, Until PD

Other Names:

BMS-844203

Active Comparator: Arm 2

Irinotecan/5-Fluorouracil(bolus)/5-Fluorouracil(infusional)/Leucovorin calcium /Bevacizumab/Bevacizumab Placebo(saline solution)

Drug: Irinotecan

Solution, IV, 180 mg/m2, Q14 days, Until PD

Other Names:

Camptosar

Drug: 5-Fluorouracil (bolus)

Solution, IV, 400 mg/m2, Q14 days, Until PD

Drug: 5-Fluorouracil (infusional)

Solution, IV, 2400 mg/m2, Q14 days, Until PD

Drug: Leucovorin calcium

Solution, IV, 400 mg/m2, Q14 days, Until PD

Drug: Bevacizumab

Solutions, IV, 5 mg/kg, Q14 days, Until PD

Other Names:

Avastin

Drug: Bevacizumab Placebo (saline solution)

Solution, IV, 0 mg/kg, On day 8 of a 2-week cycle, Until PD

Other Names:

Saline Solution

Outcome Measures

Primary Outcome Measures

Progression free survival based on tumor assessments (CT/MRI) [Every 6 weeks until documented progressive disease, initiation fo subsequent therapy for colorectal cancer, or withdrawal of consent]

Secondary Outcome Measures

Overall survival (OS), defined as the time the subject is randomized until death, in each arm [every 12 weeks]
Objective tumor response rate (ORR), defined as the proportion of randomized subjects in each arm whose best response is CR (complete response) or PR (partial response) using RECIST guidelines as determined by the site investigator [every 6 weeks]
Safety in the CT-322 plus irinotecan, 5-FU and leucovorin arm as measured by incidence of serious and non-serious adverse events, significant laboratory evaluations and significant physical examination findings in subjects [weekly]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

ECOG Performance Status (PS) ≤1
Histologically or cytologically confirmed, unresectable metastatic colorectal cancer
Measurable disease by RECIST guidelines
Evidence of disease progression following first-line therapy with a fluoropyrimidine, oxaliplatin, and bevacizumab (≤ 8 weeks since last dose)
Available paraffin embedded tumor tissue
Willing to give a whole blood sample for the study of proteins and genetic polymorphisms

Exclusion Criteria:

Less than 28 days elapsed since major surgery at time of randomization
Known CNS metastases
Excessive risk of bleeding (including use of therapeutic anticoagulation other than low dose aspirin) and history of thrombotic or embolic cerebrovascular accident
Uncontrolled hypertension
Clinically significant cardiovascular disease
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
Serious non-healing wound, active peptic ulcer, non-healing bone fracture, or bleeding skin metastasis
Known HIV Positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Acrc/Arizona Clinical Research Center, Inc.	Tucson	Arizona	United States	85715
2	Compassionate Cancer Care Medical Group Inc	Fountain Valley	California	United States	92708
3	Compassionate Cancer Care Medical Group, Inc	Riverside	California	United States	92501
4	Sharp Memorial Hospital	San Diego	California	United States	92123
5	Florida Cancer Specialists	Fort Myers	Florida	United States	33916
6	Midwest Center For Hematology/Oncology	Joliet	Illinois	United States	60432
7	Cancer Center Of Kansas	Wichita	Kansas	United States	67214
8	Gurtler, Jayne	Metairie	Louisiana	United States	70006
9	Guthrie Clinic, Ltd	Sayre	Pennsylvania	United States	18840
10	Pharma Resource	East Providence	Rhode Island	United States	02915
11	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
12	University Of Texas M.D. Anderson Cancer Center	Houston	Texas	United States	77030
13	Local Institution	Bahia Blanca	Buenos Aires	Argentina	8000
14	Local Institution	Capital Federal	Buenos Aires	Argentina	1426
15	Local Institution	Terni		Italy	05100