Suramin and Either Docetaxel or Gemcitabine in Treating Patients With Stage IIIB or Stage IV Platinum-Refractory Non-Small Cell Lung Cancer

NCT ID: NCT00066768

Last Updated: 2013-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-07-31

Brief Summary

This randomized phase I trial is studying the side effects and best dose of suramin when given together with either docetaxel or gemcitabine in treating patients with stage IIIB or stage IV non-small cell lung cancer that is refractory to platinum chemotherapy (such as cisplatin, carboplatin, or oxaliplatin). Drugs used in chemotherapy such as docetaxel and gemcitabine use different ways to stop tumor cells from dividing so they stop growing or die. Some tumors become resistant to chemotherapy drugs. Combining suramin with either docetaxel or gemcitabine may reduce resistance to the drugs and kill more tumor cells.

Detailed Description

OBJECTIVES:

I. Determine the safety of low-dose suramin administered with docetaxel or gemcitabine in patients with stage IIIB or IV platinum-refractory non-small cell lung cancer.

II. Determine, preliminarily, the antitumor activity of these regimens in these patients.

III. Determine whether suramin plasma concentrations in combination with docetaxel or gemcitabine can be predicted by pretreatment dose calculations based on clinical parameters.

OUTLINE: This is a randomized, pilot, dose-finding study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive low-dose suramin IV over 30 minutes and docetaxel IV over 1 hour on day 1.

ARM II: Patients receive low-dose suramin IV over 30 minutes and gemcitabine IV over 30 minutes on days 1 and 8.

In both arms, treatment repeats every 3 weeks for 3 courses in the absence of unacceptable toxicity. Patients with complete or partial response after the initial 3 courses optionally continue the same therapy for 3 additional courses. Patients with disease progression after 6 courses of treatment on the original arm may cross over and receive treatment on the other arm. Patients with progressive disease or stable disease after the initial 3 courses cross over to the other arm and receive treatment on that arm for 3 additional courses. Patients with responsive or stable disease after the sixth course may continue therapy on that arm.

Cohorts of 6-12 patients in each arm receive doses of suramin calculated from a clinical formula validated in prior clinical trials. Adjustments on the suramin dose are performed if the initial dose is off target and less than 50 µM peak concentration. The optimal dose is defined as the dose at which at least 5 of 6 patients achieve optimal plasma concentrations of suramin and no more than 1 of 6 patients experiences dose-limiting toxicity. In the event of dose-limiting toxicity, doses of docetaxel and gemcitabine are adjusted until the optimal dose in combination with suramin is determined.

Patients are followed for at least 30 days.

Conditions

Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

Patients receive low-dose suramin IV over 30 minutes and docetaxel IV over 1 hour on day 1.

Group Type: EXPERIMENTAL

suramin

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Arm II

Patients receive low-dose suramin IV over 30 minutes and gemcitabine IV over 30 minutes on days 1 and 8.

Group Type: EXPERIMENTAL

suramin

Intervention Type: DRUG

Given IV

gemcitabine hydrochloride

Intervention Type: DRUG

Given IV

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

suramin

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

gemcitabine hydrochloride

Given IV

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

309 F; Antrypol; Bayer 205; Fourneau 309; Germanin; RP 56976; Taxotere; TXT; dFdC; difluorodeoxycytidine hydrochloride; gemcitabine; Gemzar; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically confirmed non-small cell lung cancer

• Stage IIIB* or IV
• Progressive disease after prior platinum-containing regimen (e.g., cisplatin, carboplatin, or oxaliplatin)
• No known brain or leptomeningeal disease, unless all of the following are true:

• Lesions were previously irradiated
• No concurrent corticosteroids
• No clinical symptoms
• Performance status - ECOG 0-2
• At least 12 weeks
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL
• Bilirubin no greater than 1.5 mg/dL
• AST/ALT no greater than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• Creatinine no greater than 2.0 mg/dL
• No myocardial infarction within the past 6 months
• No congestive heart failure requiring therapy
• No unstable angina
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active serious infectious process
• No grade 2 or greater neuropathy
• No uncontrolled diabetes mellitus
• No psychiatric disorder that would preclude giving informed consent or interfere with study follow-up
• See Disease Characteristics
• At least 28 days since prior cytotoxic chemotherapy and recovered
• No more than 2 prior chemotherapy regimens
• No prior docetaxel
• No prior gemcitabine
• See Disease Characteristics
• See Disease Characteristics
• Prior radiotherapy allowed
• At least 2 weeks since prior epidermal growth factor receptor therapy
• Prior suramin allowed
• No concurrent anti-HIV medications for HIV-positive patients

• 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

Miguel Villalona-Calero

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

5889

Identifier Type: -

Identifier Source: secondary_id

CDR0000318808

Identifier Type: -

Identifier Source: secondary_id

NCI-5889

Identifier Type: -

Identifier Source: secondary_id

OSU-0238

Identifier Type: -

Identifier Source: secondary_id

2003C0022

Identifier Type: -

Identifier Source: secondary_id

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01440

Identifier Type: -

Identifier Source: org_study_id