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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase I/II Study of Suramin in Combination With Paclitaxel in Advanced (Stage IIIB or IV) Metastatic Breast Cancer

Conditions
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Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IV Breast Cancer

Intervention / Treatment
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* Drug: suramin
* Drug: paclitaxel
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (suramin and paclitaxel)<br>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. | Drug: suramin<br>* Given IV<br>* Other names: Germanin;Drug: paclitaxel<br>* Given IV<br>* Other names: Taxol;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients That Achieved Target Suramin Concentrations in Plasma | Target suramin concentration was considered achieved, if at least 5 of 6 patients achieved the target plasma concentration of 10-50 µM over the duration of 8-48 hours when paclitaxel levels are therapeutic. | Up to 5 years | 
| Objective Response Rate (Complete Response and Partial Response) as Measured by RECIST Criteria (Phase II) | Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0) for target lesion s and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR. | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response as Measured by RECIST Criteria | Evaluation of secondary endpoints will be primarily descriptive. Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data. Response rates will include 95% confidence limits. | Up to 5 years |