Metastatic Breast Cancer
Conditions
Keywords
Breast cancer, Triple negative
Brief summary
Taxanes (such as paclitaxel) are highly active to treat breast cancer. Abraxane® (nanoparticle albumin-bound paclitaxel) compared to standard paclitaxel improves efficacy and tolerability. When combined with a taxane, platinum agents improve response in metastatic breast cancer, with carboplatin conferring less toxicity than cisplatin. The investigators hypothesize that the combination of weekly Abraxane® and carboplatin will lengthen time to progression without producing intolerable toxicity.
Detailed description
Paclitaxel and cisplatin are well-recognized for their activity in treating a variety of tumors including breast cancer. As cytotoxins, they have been studied alone and in combination with other chemotherapeutic agents, and have been incorporated into treatment regimens for women who fail previous anthracycline-based therapies. Although both agents are notable for favorable response rates, they are also associated with a variety of adverse events, some of which may be dose-limiting and having a negative effect on quality of life: myelosuppression, nausea and vomiting, diarrhea, stomatitis/mucositis, short- and long-term neuropathy, nephrotoxicity, alopecia and hypersensitivity reactions. As second-generation compounds, Abraxane® and carboplatin have been shown to improve response rates and may mediate some of the toxicities associated with paclitaxel and cisplatin, respectively. Of particular interest is Abraxane's potential to reduce allergic reactions associated with other taxanes. This study combines these two agents: primarily, to evaluate progression-free survival; and secondarily, to assess the feasibility and tolerability of this regimen to treat poor prognosis metastatic breast cancer patients.
Interventions
DRUGAbraxane
Abraxane® 100 mg/m2 IV over 30 min days 1,8,15 every 28 days
DRUGCarboplatin
area under curve(AUC)=2 over 15 minutes days 1,8,15 every 28 days
Sponsors
Celgene Corporation
Duke University
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 with histologically or cytologically confirmed diagnosis of metastatic (Stage IV) breast cancer; * Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST); * Triple negative disease defined as tumor demonstrating no expression for estrogen, progesterone or HER2 receptors. (No expression is categorized as ≤ 10% of cells staining or Allred ≤ 2); * Aged 18 years or older; * Eastern Cooperative Oncology Group (ECOG)ECOG/Zubrod performance status of 0 or 1; life expectancy ≥ 3 months; * No prior chemotherapy for metastatic disease. * At least 6 months must have elapsed since prior adjuvant chemotherapy. * Laboratory tests performed within 14 days of study entry showing: * Granulocytes ≥ 1,500/µL; * Platelets ≥ 100,000/µL; * Hemoglobin ≥ 9.0 gm/dL; * Total bilirubin ≤ institutional upper limit of normal (ULN); * Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times ULN; * Alkaline phosphatase ≤ 5 times ULN; * Estimated creatinine clearance ≥ 60 mL/min. * Urine protein:creatinine ratio ≤ 1.0. or 24 hour urine protein collection demonstrating ≤ 1 gram of protein per 24 hours to be eligible. * left ventricular ejection fraction (LVEF) ≥ 50% by multiple gated acquisition scan (MUGA)/Echocardiogram; * Informed consent to receive protocol treatment: * Cognitive and communication skills adequate to comply with study and/or follow-up procedures; * Geographic proximity and ability to comply with weekly study visits for the duration of the treatment; * No reproductive potential: * If pre-menopausal - Negative serum pregnancy test within 3 days prior to initiation of protocol-based treatment and patient agrees to use contraceptive method (abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during and for 3 months after completion of protocol treatment; * If post-menopausal - Amenorrhea for ≥ 12 months or follicle stimulating hormone (FSH) within post menopausal range.
Exclusion criteria
* Pregnant or breast feeding. * Prior treatment with Abraxane® or carboplatin. * Prior chemotherapy for metastatic breast cancer. * Known hypersensitivity to any component of any study drug. * Active infection. * Current neuropathy ≥ grade 2. * central nervous system (CNS) metastases as determined by head CT with contrast or head MRI. * Uncontrolled congestive heart failure (CHF), or history of myocardial ischemia (MI), unstable angina, stroke, or transient ischemia within previous 6 months. * Uncontrolled serious contraindicated medical condition or illness.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS | PFS is defined as the interval from study registration to disease progression or death due to any cause, whichever comes first | The primary objective of the trial is to statistically test whether Abraxane® and carboplatin can improve progression-free survival (PFS) as compared to historical controls. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Safety and Tolerability of a Combination Regimen of Weekly Abraxane® and Carboplatin to Treat Women With Triple Negative Stage IV Metastatic Breast Cancer | 2 years | The proportion of patients experiencing any neurotoxicity will be tabulated by grade. The proportion of patients experiencing ≥ grade 3 non-hematologic toxicities (excluding neurotoxicity) and the proportion of patients experiencing ≥ grade 3 hematologic toxicities will be calculated with their exact 80% confidence intervals. |
Countries
China, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abraxane, Carboplatin Abraxane 100mg/m2 IV days 1, 8 and 15 of a 28 day cycle Carboplatin area under the concentration curve, (AUC)2 IV days 1,8, and 15 of a 28 day Cycle
Abraxane: Abraxane® 100 mg/m2 IV over 30 min days 1,8,15 every 28 days
Carboplatin: area under curve(AUC)=2 over 15 minutes days 1,8,15 every 28 days | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | progression | 2 |
| Overall Study | Withdrawal by Subject | 5 |
| Overall Study | Withdrawal by Treating Physician | 1 |
Baseline characteristics
| Characteristic | Abraxane, Carboplatin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 54.5 years STANDARD_DEVIATION 8.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment China | 7 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 6 / 10 |
Outcome results
Primary
PFS
The primary objective of the trial is to statistically test whether Abraxane® and carboplatin can improve progression-free survival (PFS) as compared to historical controls.
Time frame: PFS is defined as the interval from study registration to disease progression or death due to any cause, whichever comes first
Population: Due to insufficient accrual, data analysis was not performed.
Secondary
To Assess the Safety and Tolerability of a Combination Regimen of Weekly Abraxane® and Carboplatin to Treat Women With Triple Negative Stage IV Metastatic Breast Cancer
The proportion of patients experiencing any neurotoxicity will be tabulated by grade. The proportion of patients experiencing ≥ grade 3 non-hematologic toxicities (excluding neurotoxicity) and the proportion of patients experiencing ≥ grade 3 hematologic toxicities will be calculated with their exact 80% confidence intervals.
Time frame: 2 years
Population: Due to insufficient accrual, data analysis was not performed.