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.

Condition	Treatment or Intervention	Phase
Colorectal Carcinoma	Drug: VELCADE TM (bortezomib) for Injection, or PS-341	Phase II

Further Study Details: 

Expected Total Enrollment:  175

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his or her future medical care.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 β-human chorionic gonadotropin (β-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.

Alabama
      Cooper Green Hospital / Jefferson Clinic P.C., Birmingham,  Alabama,  35233,  United States
Arizona
      Arizona Cancer Center, Tucson,  Arizona,  85724,  United States
Arkansas
      Arkansas Cancer Center, Pine Bluff,  Arkansas,  71603,  United States
California
      Alta Bates Comprehensive Cancer Center, Berkley,  California,  94704,  United States
      USC/Norris Comprehensive Cancer Center, Los Angeles,  California,  90033,  United States
      California Cancer Center, Greenbrae,  California,  94904,  United States
      City of Hope Medical Group, Pasadena,  California,  91105,  United States
Florida
      H. Lee Moffit Cancer Center, Tampa,  Florida,  33612,  United States
Illinois
      Rush Cancer Institute, Chicago,  Illinois,  60612,  United States
Kentucky
      Kentuckiana Cancer Institute, PLLC, Louisville,  Kentucky,  40202,  United States
Michigan
      West Michigan Regional Cancer and Blood Center, Ludington,  Michigan,  49431,  United States
Missouri
      Bond Clinic Inc., Rolla,  Missouri,  65402,  United States
Nevada
      Nevada Cancer Center, Las Vegas,  Nevada,  89109,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756,  United States
New Jersey
      The Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08901,  United States
New York
      New York University, New York,  New York,  10016,  United States
      St. Lukes Rossevelt Hospital, New York,  New York,  10019,  United States
North Carolina
      UNC School of Medicine, Chapel Hill,  North Carolina,  27599,  United States
Ohio
      Ohio State University Medical Center, Columbus,  Ohio,  43210,  United States
Oregon
      Oregon Health Sciences, Portland,  Oregon,  97201,  United States
Tennessee
      Memphis Cancer Center, PC, Memphis,  Tennessee,  38119,  United States
Texas
      University of Texas Health Sciences Center at San Antonio, San Antonio,  Texas,  78229,  United States

Study ID Numbers:  M34102-049
Record last reviewed:  January 2004
Last Updated:  October 13, 2004
Record first received:  January 21, 2003
ClinicalTrials.gov Identifier:  NCT00051987
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08