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

NCT ID: NCT00083109

Last Updated: 2015-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2008-03-31

Brief Summary

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

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.

Conditions

Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Fluorouracil

Intervention Type: DRUG

Given IV

Pharmacological Study

Intervention Type: OTHER

Correlative studies

Suramin

Intervention Type: DRUG

Given IV

Interventions

Fluorouracil

Given IV

Intervention Type: DRUG

Pharmacological Study

Correlative studies

Intervention Type: OTHER

Suramin

Given IV

Intervention Type: DRUG

Other Intervention Names

5-Fluoro-2,4(1H, 3H)-pyrimidinedione; 5-Fluorouracil; 5-Fluracil; 5-FU; AccuSite; Actino-Hermal; Adrucil; Arumel; Cytosafe; Efudex; Efurix; Fiverocil; Fluoro Uracil; Fluoroplex; Fluouracil; Flurablastin; Fluracedyl; Fluracil; Fluril; Fluroblastin; Flurox; Ribofluor; Ro 2-9757; Ro-2-9757; Timazin

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ronald Bukowski

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

NCI-2012-02586

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCF-6101

Identifier Type: -

Identifier Source: secondary_id

NCI-6036

Identifier Type: -

Identifier Source: secondary_id

CDR0000363559

Identifier Type: -

Identifier Source: secondary_id

CWRU-CASE-1804

Identifier Type: -

Identifier Source: secondary_id

IRB 6101

Identifier Type: OTHER

Identifier Source: secondary_id

6036

Identifier Type: OTHER

Identifier Source: secondary_id

R01CA093871

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062502

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-02586

Identifier Type: -

Identifier Source: org_study_id