Fluorouracil and Low-Dose Suramin as Chemosensitization in Treating Patients With Metastatic Renal Cell (Kidney) Cancer

PRIMARY OBJECTIVES:

I. Determine the dose of suramin and fluorouracil that would result in plasma concentrations of suramin between 10-50 uM in patients with metastatic renal cell cancer. (Phase I) II. Determine the objective response rate (complete response and partial response) in patients treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the preliminary efficacy of this regimen in these patients. (Phase I) II. Determine the pharmacokinetics of low-dose suramin in these patients. (Phase I) III. Determine the time to tumor progression and progress rate at 3 and 6 months in patients treated with this regimen. (Phase II)

OUTLINE: This is a dose-escalation phase I study followed by a phase II study.

PHASE I: Patients receive suramin IV over 30 minutes and fluorouracil IV on days 1, 8, 15, 22, 29, and 36. Cohorts of 3-6 patients receive escalating doses suramin and fluorouracil until the dose level allowing 10-50 uM of suramin into the patient's blood is determined without 2 or more of 6 patients experiencing dose-limiting toxicity.

PHASE II: Patients receive suramin and fluorouracil (at the dose level determined in phase I) as in phase I.

In both phases, courses repeat every 8 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.

Patients are followed for survival.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.

Inclusion criteria

• Histologically confirmed renal cell cancer

• Metastatic disease
• Measurable or evaluable disease

• Measurable disease required for phase II
• No untreated CNS metastasis or CNS metastases progressing ≤ 4 weeks after prior radiotherapy
• Performance status - ECOG 0-1
• At least 12 weeks
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9.0 g/dL
• AST ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN
• Bilirubin ≤ 1.5 mg/dL
• Creatinine ≤ 1.8 mg/dL
• Calcium ≤ ULN
• No untreated hypercalcemia
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must be surgically sterile or use effective contraception
• No uncontrolled diabetes mellitus
• No known severe hypersensitivity to suramin
• No other concurrent uncontrolled illness
• No active or ongoing infection
• No active autoimmune disease
• No neuropathy ≥ grade 2
• No psychiatric illness or social situation that would preclude study compliance
• No other malignancy within the past 5 years except basal cell skin cancer, carcinoma in situ of the cervix, or localized prostate cancer
• No concurrent filgrastim (G-CSF)
• No more than 2 prior chemotherapy regimens for renal cell cancer (phase II only)
• No concurrent corticosteroid dose more than physiologic replacement levels
• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy
• Recovered from prior oncologic or other major surgery
• At least 4 weeks since prior major surgery
• No concurrent surgery
• Recovered from all prior anticancer therapy other than alopecia (chronic toxicity < grade 2)
• At least 4 weeks since prior systemic therapy
• More than 30 days since prior investigational drugs
• Concurrent bisphosphonates allowed