Colorectal Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum
Brief 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.
Detailed description
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.
Interventions
DRUGbrivudine phosphoramidate
Sponsors
NewBiotics
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed