Clinical trial NCT00054028: Suramin and Paclitaxel in Treating Women With Stage IIIB-IV Breast Cancer
Official title: A Phase I/II Study of Suramin in Combination With Paclitaxel in Advanced (Stage IIIB or IV) Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IV Breast Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-02-06
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percentage of Patients That Achieved Target Suramin Concentrations in Plasma
timeFrame: Up to 5 years
measure: Objective Response Rate (Complete Response and Partial Response) as Measured by RECIST Criteria (Phase II)
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Response as Measured by RECIST Criteria
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
Study officials:
affiliation: Ohio State University
name: Charles Shapiro
role: PRINCIPAL_INVESTIGATOR
References: