Suramin and Paclitaxel in Treating Women With Stage IIIB-IV Breast Cancer

NCT ID: NCT00054028

Last Updated: 2015-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-31
• Study Completion Date: 2008-03-31

Brief Summary

This phase I/II trial studies the best dose of suramin when given together with paclitaxel in treating women with stage IIIB-IV breast cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Suramin may increase the effectiveness of paclitaxel by making tumor cells more sensitive to the drug.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the dose of suramin in combination with paclitaxel (TXT) that results in suramin plasma concentrations approaching 10-50 uM over the duration, when TXT in the plasma is at therapeutically significant levels, in women with stage IIIB or IV breast cancer. (Phase I) II. Determine the objective response rate in patients treated with this regimen. (Phase II)

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of low-dose suramin in these patients. (Phase I) II. Determine the time to tumor progression in patients treated with this regimen. (Phase II) III. Determine the 1-year survival of patients treated with this regimen. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of suramin followed by a phase II multicenter study.

PHASE I: Patients receive low-dose suramin intravenously (IV) over 30 minutes and paclitaxel IV over 1 hour once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive adjusted doses of suramin until a target dose is determined. The suramin target dose is defined as the dose at which at least 5 of 6 patients achieve the target plasma concentration of 10-50 uM over the duration when paclitaxel levels are therapeutic.

PHASE II: Patients receive paclitaxel in combination with the target dose of suramin as above.

PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for the phase I study within 9 months. A total of 28 patients will be accrued for the phase II study within 18-24 months.

Conditions

Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer

Study Design

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

Study Groups

Treatment (suramin and paclitaxel)

PHASE I: Patients receive low-dose suramin IV over 30 minutes and paclitaxel IV over 1 hour once weekly. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive adjusted doses of suramin until a target dose is determined. The suramin target dose is defined as the dose at which at least 5 of 6 patients achieve the target plasma concentration of 10-50 uM over the duration when paclitaxel levels are therapeutic.

PHASE II: Patients receive paclitaxel in combination with the target dose of suramin as above.

Group Type: EXPERIMENTAL

suramin

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

pharmacological study

Intervention Type: OTHER

Correlative studies

Interventions

suramin

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

Other Intervention Names

309 F; Antrypol; Bayer 205; Fourneau 309; Germanin; Anzatax; Asotax; TAX; Taxol; pharmacological studies

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed stage IIIB or IV metastatic breast cancer (MBC)
• Prior chemotherapy:

• Phase I: patients must have received prior paclitaxel or other taxanes in either the adjuvant or metastatic setting; prior chemotherapy, radiation or surgery must be completed at least 21 days before study entry; prior treatment with anthracyclines is not required
• Phase II: up to two prior chemotherapy regimens for stage IIIB or IV MBC; patients must have received prior paclitaxel or other taxanes in either the adjuvant or metastatic setting; prior chemotherapy, radiation or surgery must be completed at least 21 days before study entry; prior treatment with anthracyclines is not required
• Measurable disease (phase II)
• No known brain metastases
• Hormone receptor status:

• Not specified
• Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
• White blood cell (WBC) at least 3,000/mm^3
• Absolute neutrophil count at least 1,000/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
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) no greater than 2.5 times upper limit of normal
• Creatinine no greater than 1.5 mg/dL
• Left ventricular ejection fraction (LVEF) at least lower limit of normal
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reactions attributable to compounds of similar chemical or biological composition to Cremophor
• No concurrent uncontrolled illness that would preclude study compliance
• No ongoing or active infection
• No uncontrolled diabetes mellitus
• No psychiatric illness or social situations that would preclude study compliance
• No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• See Disease Characteristics
• At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No more than 2 prior chemotherapy regimens for this malignancy (phase II)
• No concurrent steroids or hormones except the following:

• Steroids to prevent hypersensitivity reactions prior to paclitaxel administration
• Hormones for nondisease-related conditions (e.g., insulin for diabetes)
• At least 3 weeks since prior radiotherapy and recovered
• At least 3 weeks since prior surgery and recovered
• No concurrent combination antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
• No other concurrent investigational agents
• Concurrent bisphosphonates (i.e., pamidronate or zoledronate) are allowed for the treatment of hypercalcemia or palliation of skeletal metastases

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Shapiro

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Ohio State University Medical Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

0216

Identifier Type: -

Identifier Source: secondary_id

OSU-02H0216

Identifier Type: -

Identifier Source: secondary_id

OSU-0216

Identifier Type: -

Identifier Source: secondary_id

NCI-5851

Identifier Type: -

Identifier Source: secondary_id

CDR0000269707

Identifier Type: -

Identifier Source: secondary_id

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01431

Identifier Type: -

Identifier Source: org_study_id