In this Phase II trial, the investigators will evaluate the combination of gemcitabine, carboplatin, and panitumumab in the treatment of patients with metastatic triple-negative breast cancer. In addition, to assess the efficacy of this combination, tumor tissue will be examined for the presence of various markers, including K-ras and PI3K-activating mutations, EGFR, PTEN, and p53. Correlation of tumor response with marker expression may define a patient subset that is particularly responsive to treatment with a panitumumab-containing combination.
All patients will receive a pre-emptive skin care regimen during panitumumab therapy to reduce skin toxicity. Treatment cycles will be repeated every 14 days (2 weeks). During each treatment, panitumumab will be administered first, then carboplatin, then gemcitabine. All drugs will be administered according to standard guidelines. Patients will be re-evaluated for response after completion of 3 cycles (6 weeks) of treatment. Patients with objective response or stable disease will continue treatment. Subsequent re-evaluations will occur every 6 weeks. Patients will continue treatment with all three drugs until tumor progression, or until unacceptable toxicity occurs. If patients experience toxicity caused by gemcitabine/carboplatin and are continuing to benefit from treatment, panitumumab can be continued as a single agent (at the same dose and schedule), at the discretion of the investigator, until disease progression occurs.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
71
6 mg/kg IV on Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
AUC=2.5 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
1500 mg/m2 IV, Day 1 of each 2-week treatment cycle for 3 cycles (6 weeks)
Los Robles
Thousand Oaks, California, United States
Aventura Hospital and Medical Center
Aventura, Florida, United States
Progression-free Survival (PFS)
Measured from Day 1 of study drug administration to disease progression - defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a 20% increase in the sum of the longest diameter of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions
Time frame: every 6 weeks until treatment discontinuation
Objective Response Rate and Clinical Benefit Rate
Estimated as the proportion of subjects who meet the criteria for complete or partial response (CR or PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 - for target lesions assessed by MRI: Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: every 6 weeks until treatment discontinuation
Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity
Assessments made through analysis of treatment-related adverse events and serious adverse events
Time frame: every 6 weeks until discontinuation of treatment, expected average of 18 months
Correlation of Biomarker Expressions of EGFR, K-ras, p53, PTEN Expression, and PI3K in Triple-negative Breast Cancer With Response to Treatment With the Combination of Gemcitabine, Carboplatin, and Panitumumab
Median PFS (95% CI), months, reported by biomarker expression/mutation status for: EGFR, p53, PTEN, PIK3CA, KRAS
Time frame: 18 months
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