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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00083109
First received: May 14, 2004
Last updated: January 16, 2013
Last verified: January 2013

May 14, 2004
January 16, 2013
March 2004
March 2008   (final data collection date for primary outcome measure)
  • Dose of suramin to deliver the target plasma concentrations of 10 to 50 uM (Phase I) [ Time Frame: Up to 48 hours ] [ Designated as safety issue: No ]
  • Objective response rate (CR + PR) using RECIST criteria (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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.
Not Provided
Complete list of historical versions of study NCT00083109 on ClinicalTrials.gov Archive Site
  • Time to disease progression (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    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.
  • Progression rate (Phase II) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.
  • Progression rate (Phase II) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.
  • Toxicity assessed using NCI CTCAE version 3.0 (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    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.
Not Provided
Not Provided
Not Provided
 
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

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.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Drug: suramin
    Given IV
    Other Names:
    • 309 F
    • Antrypol
    • Bayer 205
    • Fourneau 309
    • Germanin
  • Drug: fluorouracil
    Given IV
    Other Names:
    • 5-fluorouracil
    • 5-Fluracil
    • 5-FU
  • Other: pharmacological study
    Correlative studies
    Other Name: pharmacological studies
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.

Interventions:
  • Drug: suramin
  • Drug: fluorouracil
  • Other: pharmacological study
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
36
Not Provided
March 2008   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00083109
NCI-2012-02586, IRB 6101, U01CA062502, R01CA093871, CDR0000363559
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Ronald Bukowski The Cleveland Clinic
National Cancer Institute (NCI)
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP