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.

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