Clinical trial NCT00083109: Fluorouracil and Low-Dose Suramin as Chemosensitization in Treating Patients With Metastatic Renal Cell (Kidney) Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Renal Cell Carcinoma
Stage IV Renal Cell Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-05-17
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Dose of suramin to deliver the target plasma concentrations of 10 to 50 uM (Phase I)
timeFrame: Up to 48 hours
measure: Objective response rate (CR + PR) using RECIST criteria (Phase II)
timeFrame: Up to 4 years
Secondary outcomes:
measure: Progression rate (Phase II)
timeFrame: 3 months
measure: Progression rate (Phase II)
timeFrame: 6 months
measure: Time to disease progression (Phase II)
timeFrame: Up to 4 years
measure: Toxicity assessed using NCI CTCAE version 3.0 (Phase II)
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Ronald Bukowski
role: PRINCIPAL_INVESTIGATOR
References: