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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Stage IV Renal Cell Cancer; Recurrent Renal Cell Carcinoma

Treatments: Drug: Suramin; Other: Pharmacological Study; Drug: Fluorouracil

Study type: Interventional

Funder types: NIH

Identifiers

NCT00083109

U01CA062502 (U.S. NIH Grant/Contract)

CWRU-CASE-1804

R01CA093871 (U.S. NIH Grant/Contract)

IRB 6101 (Other Identifier)

6036 (Other Identifier)

NCI-2012-02586 (Registry Identifier)

CDR0000363559

NCI-6036

CCF-6101

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 36 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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36 participants in 1 patient group

Treatment (suramin and fluorouracil)

Experimental group

Description:

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.

Treatment:

Drug: Suramin

Drug: Fluorouracil

Other: Pharmacological Study