nb1011 in treating patients with metastatic or recurrent colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase i/ii trial to study the effectiveness of nb1011 in treating patients who have metastatic or recurrent colorectal cancer that has not responded to previous treatment.

objectives: * determine the maximum tolerated dose of nb1011 in patients with fluoropyrimidine-resistant metastatic or recurrent colorectal cancer. * determine the safety and toxic effects of this drug in these patients. * determine the pharmacokinetics of this drug in these patients. * determine the efficacy of this drug in these patients. outline: this is a phase i dose-escalation study followed by a phase ii study. * phase i: patients receive nb1011 iv over 1 hour on days 1-5. treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. cohorts of 3-6 patients receive escalating doses of nb1011 until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. * phase ii: additional patients receive nb1011 at the mtd as in phase i. patients are followed at day 30 and then for 5 months. projected accrual: a maximum of 25 patients will be accrued for the phase i portion of this study. a total of 15-25 patients will be accrued for the phase ii portion of this study.

Eligibility criteria:
disease characteristics: * histologically or cytologically confirmed metastatic or recurrent colorectal adenocarcinoma that has progressed during or within 6 months of fluoropyrimidine-based therapy * prior treatment with irinotecan with or without fluorouracil * evaluable or measurable disease * uni-dimensionally measurable disease allowed provided cea is at least 2 times the upper limit of normal * no meningeal or cns metastases or carcinomatous meningitis patient characteristics: age: * 18 and over performance status: * karnofsky 70-100% life expectancy: * at least 3 months hematopoietic: * wbc at least 3,000/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin less than 1.5 mg/dl (regardless of liver metastases) * ast and alt less than 1.5 times upper limit of normal (uln) (3 times uln if liver metastases present) * pt and inr normal * ptt normal renal: * creatinine less than 1.5 mg/dl or * creatinine clearance greater than 50 ml/min other: * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * hiv negative * no known hypersensitivity to nb1011 or any excipient or vehicle in its formulation * no active or uncontrolled serious bacterial, viral, fungal, or parasitic infection * no prior or concurrent alcohol abuse or dependency * no other malignancy within the past 2 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * no concurrent medical or psychological condition that would preclude study prior concurrent therapy: biologic therapy: * not specified chemotherapy: * see disease characteristics * recovered from prior anticancer chemotherapy * no concurrent fluoropyrimidine-based or thymidylate synthase inhibitor agents endocrine therapy: * not specified radiotherapy: * recovered from prior anticancer radiotherapy * no concurrent radiotherapy except palliative radiotherapy (to control a fracture or pain) provided index lesions are not involved surgery: * recovered from prior anticancer surgery other: * at least 30 days since prior investigational agents * no other concurrent anticancer therapy * no concurrent disulfiram

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