Phase 2b Study of VELCADE Alone and VELCADE Plus Irinotecan in Patients With Relapsed or Refractory Colorectal Carcinoma

Colorectal Carcinoma Clinical Trial

Official title:

A Randomized, Multicenter, Open-Label, Phase 2b Study of VELCADE Alone and VELCADE Plus Irinotecan in Patients With Relapsed or Refractory Colorectal Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00051987
• Other study ID #: M34102-049
• Status: Completed
• Phase: Phase 2
• First received: January 21, 2003
• Last updated: February 7, 2008
• Start date: December 2002

Study information

• Verified date: February 2008
• Source: Millennium Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate how tumors in patients with colorectal carcinoma respond to treatment with VELCADE alone versus VELCADE given with irinotecan, and also to see what effects (good and bad) it has on you and your cancer.

Description:

In this study, patients with colorectal cancer that is no longer responding to standard medical treatment with irinotecan or an irinotecan containing treatment will be randomized to treatment with VELCADE alone or to treatment with VELCADE in combination with irinotecan.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Patient has histologically confirmed inoperable locally advanced or metastatic CRC.

• Patient has measurable disease.

• Patient is not considered a candidate for immediate curative resection.

• Patient has received no more than 2 prior treatment regimens for metastatic disease, one of which must have contained irinotecan.

• Patient has relapsed or progressed while receiving an irinotecan-containing regimen.

• Patient has KPS of 70% or greater.

• Patient has a life expectancy greater than 3 months.

• Patient is 18 years of age or older.

• Female patient is postmenopausal, surgically sterilized, or willing to use an acceptable method of birth control (ie, a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.

• Male patient agrees to use an acceptable method of birth control for the duration of the study.

• Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his or her future medical care.

• Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.

Exclusion Criteria

• Patient has greater than or equal to Grade 2 neuropathy as defined by the NCI Common Toxicity Criteria (CTC):

• Grade 2: Objective sensory loss or paresthesia (including tingling), interfering with function, but not interfering with activities of daily living (ADL).

• Grade 3: Sensory loss or paresthesia interfering with ADL.

• Grade 4: Permanent sensory loss that interferes with function.

• Patient has previously received treatment with VELCADE.

• Patient has other malignancies except non-melanoma skin cancers and carcinoma of the cervix in situ.

• Patient has received chemotherapy within 4 weeks prior to enrollment.

• Patient has received radiation therapy within 4 weeks prior to enrollment.

• Patient has received monoclonal antibodies within 6 weeks prior to enrollment.

• Patient had major surgery within 4 weeks prior to enrollment.

• Patient has inadequate organ function at Baseline (ie, Day 1 of Cycle 1) as defined by the following laboratory values:

• Platelet count = 100,000 x 109/L

• Hemoglobin = 8.0 g/dL

• Absolute neutrophil count (ANC) = 1.5 x 109/L

• Aspartate transaminase (AST) = 3 times the upper limit of the normal range (ULN)

• Alanine transaminase (ALT) = 3 times ULN

• Total bilirubin = 1.5 times ULN, unless clearly related to the disease

• Calculated or measured creatinine clearance = 60 mL/minute.

• Patient has had a myocardial infarction within 6 months of enrollment or has New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at Screening has to be documented by the investigator as not medically relevant.

• Patient has symptomatic brain metastases.

• Patient has an active systemic infection requiring treatment.

• Patient has a history of inflammatory bowel disease.

• Patient has a history of allergic reaction attributable to compounds containing boron or mannitol.

• Patient previously required premature discontinuation of irinotecan therapy because of drug-related toxicity.

• Patient is known to be human immunodeficiency virus (HIV)-positive. Patients assessed by the investigator to be at risk for HIV infection should be tested in accordance with local regulations.

• Patient is known to be hepatitis B surface antigen-positive or has known active hepatitis C infection. Patients assessed by the investigator to be at risk for hepatitis B or C infection should be tested in accordance with local regulations.

• Patient has poorly controlled hypertension, diabetes mellitus, or another serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

• Female patient is pregnant or breast-feeding. Confirmation that the patient is not pregnant must be established by a negative serum ß-human chorionic gonadotropin (ß-hCG) pregnancy test result obtained during the Screening period. Pregnancy testing is not required for postmenopausal or surgically sterilized women.

• Patient currently is enrolled in another clinical research study or has received an investigational agent for any reason within 4 weeks of enrollment.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Carcinoma
• Colorectal Neoplasms

Intervention

Drug:
• VELCADE TM (bortezomib) for Injection, or PS-341

Locations

Country	Name	City	State
United States	Alta Bates Comprehensive Cancer Center	Berkley	California
United States	Cooper Green Hospital / Jefferson Clinic P.C.	Birmingham	Alabama
United States	UNC School of Medicine	Chapel Hill	North Carolina
United States	Rush Cancer Institute	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	California Cancer Center	Greenbrae	California
United States	Nevada Cancer Center	Las Vegas	Nevada
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	USC/Norris Comprehensive Cancer Center	Los Angeles	California
United States	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky
United States	West Michigan Regional Cancer and Blood Center	Ludington	Michigan
United States	Memphis Cancer Center, PC	Memphis	Tennessee
United States	The Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	New York University	New York	New York
United States	St. Lukes Rossevelt Hospital	New York	New York
United States	City of Hope Medical Group	Pasadena	California
United States	Arkansas Cancer Center	Pine Bluff	Arkansas
United States	Oregon Health Sciences	Portland	Oregon
United States	Bond Clinic Inc.	Rolla	Missouri
United States	University of Texas Health Sciences Center at San Antonio	San Antonio	Texas
United States	H. Lee Moffit Cancer Center	Tampa	Florida
United States	Arizona Cancer Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States,