Phase I/II Trial Of Low Dose Suramin (CI-1003, NSC#34936) And 5-Fluorouracil In Patients With Metastatic Renal Cell Carcinoma (RCC)
Phase I/II Trial Of Low Dose Suramin (CI-1003, NSC#34936) And 5-Fluorouracil In Patients With Metastatic Renal Cell Carcinoma (RCC)
Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Suramin may increase the effectiveness of fluorouracil by making tumor cells more sensitive to the drug. This phase I/II trial is studying the side effects and best dose of fluorouracil and the chemosensitizer suramin and to see how well they work 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
Measurable or evaluable disease
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