Title
NB1011 in Treating Patients With Metastatic or Recurrent Colorectal Cancer
A Phase I/II Study Of NB1011 Administered Intravenously Daily For 5 Days Every 4 Weeks In Fluoropyrimidine-Resistant Metastatic Or Relapsed Colorectal Cancers
Phase
Phase 1/Phase 2Lead Sponsor
NewBioticsStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Colorectal CancerIntervention/Treatment
brivudine phosphoramidate ...Study Participants
NoneRATIONALE: 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.
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
