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

• ClinicalTrials.gov Identifier: NCT00083109
• Recruitment Status: Completed
• First Posted: May 17, 2004
• Last Update Posted: May 25, 2015
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer	Drug: Fluorouracil; Other: Pharmacological Study; Drug: Suramin	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial Of Low Dose Suramin (CI-1003, NSC#34936) And 5-Fluorouracil In Patients With Metastatic Renal Cell Carcinoma (RCC)
• Study Start Date: March 2004
• Actual Primary Completion Date: December 2005
• Actual Study Completion Date: March 2008

Arms and Interventions

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.

Drug: Fluorouracil; Given IV; Other 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; Other: Pharmacological Study; Correlative studies; Drug: Suramin; Given IV

Outcome Measures

Primary Outcome Measures :

1. Dose of suramin to deliver the target plasma concentrations of 10 to 50 uM (Phase I) [ Time Frame: Up to 48 hours ]
2. Objective response rate (CR + PR) using RECIST criteria (Phase II) [ Time Frame: Up to 4 years ]
   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.

Secondary Outcome Measures :

1. Progression rate (Phase II) [ Time Frame: 3 months ]
   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.
2. Progression rate (Phase II) [ Time Frame: 6 months ]
   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. Time to disease progression (Phase II) [ Time Frame: Up to 4 years ]
   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.
4. Toxicity assessed using NCI CTCAE version 3.0 (Phase II) [ Time Frame: Up to 4 years ]
   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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ronald Bukowski; The Cleveland Clinic

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00083109
• Other Study ID Numbers: NCI-2012-02586; NCI-2012-02586 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CCF-6101; NCI-6036; CDR0000363559; CWRU-CASE-1804; IRB 6101 ( Other Identifier: Cleveland Clinic Foundation ); 6036 ( Other Identifier: CTEP ); R01CA093871 ( U.S. NIH Grant/Contract ); U01CA062502 ( U.S. NIH Grant/Contract )
• First Posted: May 17, 2004
• Last Update Posted: May 25, 2015
• Last Verified: January 2013

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Suramin; Fluorouracil; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antinematodal Agents; Anthelmintics; Antiparasitic Agents; Anti-Infective Agents; Trypanocidal Agents; Antiprotozoal Agents