bortezomib in treating patients with metastatic or recurrent colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: bortezomib may interfere with the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. purpose: phase ii trial to study the effectiveness of bortezomib in treating patients who have metastatic or recurrent colorectal cancer.

objectives: * determine the efficacy of bortezomib, in terms of response rate and stable disease rate, in patients with recurrent or metastatic colorectal cancer. * determine the toxicity of this drug in these patients. * determine the time to progression and response duration in patients treated with this drug. * determine whether there is a relationship between levels of transcription factors nf kappa b and hif-1 alpha and clinical outcome in patients treated with this drug. outline: this is an open-label study. patients receive bortezomib iv on days 1, 4, 8, and 11. courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. projected accrual: a total of 21-41 patients will be accrued for this study within 2-4 months.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed adenocarcinoma of the colon or rectum that is incurable with conventional therapy * metastatic or recurrent disease * at least 1 unidimensionally measurable lesion * at least 20 mm by conventional techniques or at least 10 mm by spiral ct scan * disease must be accessible to biopsy * no known brain metastases patient characteristics: age * 18 and over performance status * ecog 0-1 or * karnofsky 70-100% life expectancy * more than 3 months hematopoietic * absolute granulocyte count at least 1,500/mm\^3 * wbc at least 3,000/mm\^3 * platelet count at least 100,000/mm\^3 hepatic * bilirubin no greater than 1.25 times upper limit of normal (uln) * ast or alt no greater than 3 times uln (less than 5 times uln if liver metastases present) renal * creatinine no greater than 1.25 times unl or * creatinine clearance at least 50 ml/min cardiovascular * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia other * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no psychiatric illness or social situation that would preclude study compliance * no other uncontrolled concurrent illness * no ongoing or active infection * no other active malignancy within the past 3 years except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix * no grade 1 or greater peripheral neuropathy due to prior chemotherapy * no significant traumatic injury within the past 21 days prior concurrent therapy: biologic therapy * not specified chemotherapy * no more than 1 line of prior chemotherapy (including any combination of fluorouracil, irinotecan, and/or oxaliplatin) for metastatic disease * at least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * prior adjuvant chemotherapy allowed * no concurrent cytotoxic chemotherapy radiotherapy * more than 4 weeks since prior radiotherapy and recovered * no prior radiotherapy to measurable target lesion unless disease progression has occurred after radiotherapy * no concurrent radiotherapy to the sole site of measurable disease surgery * more than 21 days since prior major surgery other * no other concurrent investigational agents * no concurrent combination antiretroviral therapy for hiv-positive patients

Keywords: stage iv colon cancer stage iv rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum recurrent colon cancer recurrent rectal cancer