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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer
• Intervention / Treatment: Other: Pharmacological Study; Drug: Fluorouracil; Drug: Suramin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (suramin and fluorouracil); 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.

Other: Pharmacological Study; Correlative studies; Drug: Fluorouracil; Given IV; Other Names: 5-FU; 5-Fluracil; Fluracil; 5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; AccuSite; Fluoro Uracil; Fluouracil; Flurablastin; Fluracedyl; Fluril; Fluroblastin; Ribofluor; Ro 2-9757; Ro-2-9757; Adrucil; Efudex; Actino-Hermal; Arumel; Cytosafe; Efurix; Fiverocil; Fluoroplex; Flurox; Timazin; Drug: Suramin; Given IV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ronald Bukowski, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: May 14, 2004
• First Submitted That Met QC Criteria: May 14, 2004
• First Posted (Estimate): May 17, 2004

Study Record Updates

• Last Update Posted (Estimate): May 25, 2015
• Last Update Submitted That Met QC Criteria: May 22, 2015
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiprotozoal Agents; Antiparasitic Agents; Antinematodal Agents; Anthelmintics; Trypanocidal Agents; Fluorouracil; Suramin
• Other Study ID Numbers: NCI-2012-02586 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062502 (U.S. NIH Grant/Contract); CCF-6101; NCI-6036; CDR0000363559; CWRU-CASE-1804; IRB 6101 (Other Identifier: Cleveland Clinic Foundation); 6036 (CTEP); R01CA093871 (U.S. NIH Grant/Contract)