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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase I/II Trial Of Low Dose Suramin (CI-1003, NSC#34936) And 5-Fluorouracil In Patients With Metastatic Renal Cell Carcinoma (RCC)

Conditions
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Recurrent Renal Cell Carcinoma, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Drug: Fluorouracil
* Other: Pharmacological Study
* Drug: Suramin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (suramin and fluorouracil)<br>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. | Drug: Fluorouracil<br>* Given IV<br>* Other names: Timazin;Other: Pharmacological Study<br>* Correlative studies<br>Drug: Suramin<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose of suramin to deliver the target plasma concentrations of 10 to 50 uM (Phase I) |  | Up to 48 hours | 
| Objective response rate (CR + PR) using RECIST criteria (Phase II) | Summary statistics (e.g. means and standard deviations or medians and ranges, or frequency counts) and 95% confidence intervals will be calculated. Graphical models will also be used to summarize the data. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression rate (Phase II) | Summary statistics (e.g. means and standard deviations or medians and ranges, or frequency counts) and 95% confidence intervals will be calculated. Graphical models will also be used to summarize the data. | 3 months | 
| Progression rate (Phase II) | Summary statistics (e.g. means and standard deviations or medians and ranges, or frequency counts) and 95% confidence intervals will be calculated. Graphical models will also be used to summarize the data. | 6 months | 
| Time to disease progression (Phase II) | Summary statistics (e.g. means and standard deviations or medians and ranges, or frequency counts) and 95% confidence intervals will be calculated. Graphical models will also be used to summarize the data. | Up to 4 years | 
| Toxicity assessed using NCI CTCAE version 3.0 (Phase II) | Summary statistics (e.g. means and standard deviations or medians and ranges, or frequency counts) and 95% confidence intervals will be calculated. Graphical models will also be used to summarize the data. | Up to 4 years |