Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IV Breast Cancer
Conditions
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.
Interventions
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients That Achieved Target Suramin Concentrations in Plasma | Up to 5 years | 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. |
| Objective Response Rate (Complete Response and Partial Response) as Measured by RECIST Criteria (Phase II) | Up to 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response as Measured by RECIST Criteria | Up to 5 years | 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. |
Countries
United States
Participant flow
Recruitment details
Phase I trial was performed at Ohio State University(OSU). Phase II, OSU was the coordinating center with other participating centers.
Pre-assignment details
Women with metastatic breast cancer
Participants by arm
| Arm | Count |
|---|---|
| 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. | 9 |
| Suramin and Paclitaxel (Phase II) Patients receive paclitaxel in combination with the target dose of suramin. | 22 |
| Total | 31 |
Baseline characteristics
| Characteristic | Suramin and Paclitaxel (Phase II) | Suramin and Paclitaxel (Phase I) | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 56 years | 56 years |
| ECOG performance status (PS) ECOG PS 0 | 11 patients | 5 patients | 16 patients |
| ECOG performance status (PS) ECOG PS 1 | 8 patients | 4 patients | 12 patients |
| ECOG performance status (PS) ECOG PS 2 | 3 patients | 0 patients | 3 patients |
| ER/PR/HER 2 neu status ER+ or PR+ Status | 14 patients | 6 patients | 20 patients |
| ER/PR/HER 2 neu status HER2 neu+ Status | 0 patients | 0 patients | 0 patients |
| ER/PR/HER 2 neu status Triple negative Status | 8 patients | 3 patients | 11 patients |
| Menopausal status Postmenopausal | 21 patients | 9 patients | 30 patients |
| Menopausal status Premenopausal | 1 patients | 0 patients | 1 patients |
| Number of sites of metastastic 1 | 9 patients | 1 patients | 10 patients |
| Number of sites of metastastic 2 | 7 patients | 5 patients | 12 patients |
| Number of sites of metastastic ≥3 | 6 patients | 3 patients | 9 patients |
| Prior chemotherapy (metastatic setting) 0 Prior chemo therapies | 0 patients | 5 patients | 5 patients |
| Prior chemotherapy (metastatic setting) 1 Prior chemo therapies | 4 patients | 10 patients | 14 patients |
| Prior chemotherapy (metastatic setting) 2 Prior chemo therapies | 3 patients | 7 patients | 10 patients |
| Prior chemotherapy (metastatic setting) 3 Prior chemo therapies | 2 patients | 0 patients | 2 patients |
| Prior taxane therapy Docetaxel | 10 patients | 5 patients | 15 patients |
| Prior taxane therapy Nab-paclitaxel | 1 patients | 0 patients | 1 patients |
| Prior taxane therapy Paclitaxel | 9 patients | 4 patients | 13 patients |
| Prior taxane therapy Paclitaxel and docetaxel | 2 patients | 0 patients | 2 patients |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 8 Participants | 27 Participants |
| Region of Enrollment United States | 22 patients | 9 patients | 31 patients |
| Sex: Female, Male Female | 22 Participants | 9 Participants | 31 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sites of metastases Bone | 11 patients | 6 patients | 17 patients |
| Sites of metastases Liver | 12 patients | 3 patients | 15 patients |
| Sites of metastases Lung | 10 patients | 6 patients | 16 patients |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 1 / 31 |
Outcome results
Primary
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.
Time frame: Up to 8 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Suramin and Paclitaxel | Objective Response Rate (Complete Response and Partial Response) as Measured by RECIST Criteria (Phase II) | Complete Response (CR) | 0 patients |
| Suramin and Paclitaxel | Objective Response Rate (Complete Response and Partial Response) as Measured by RECIST Criteria (Phase II) | Partial Response (PR) | 5 patients |
Primary
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.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suramin and Paclitaxel | Percentage of Patients That Achieved Target Suramin Concentrations in Plasma | 88 percent of patients |
Secondary
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.
Time frame: Up to 5 years
Population: Objective Response Rate
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Suramin and Paclitaxel | Response as Measured by RECIST Criteria | 23 percentage of patients |