A Phase II Trial of Panitumumab, Gemcitabine, and Carboplatin in Triple-Negative Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Panitumumab
- Conditions
- Metastatic Breast Cancer
- Sponsor
- SCRI Development Innovations, LLC
- Enrollment
- 71
- Locations
- 17
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients \>=18 years of age.
- •Histologically or cytologically confirmed diagnosis of unresectable locally advanced or stage IV breast cancer.
- •No more than 1 prior treatment regimen for metastatic breast cancer.
- •Estrogen receptor and progesterone receptor negative (defined as \<10% staining by IHC).
- •Paraffin-embedded tumor tissue (from the primary tumor or metastasis) for biomarker testing. (In the absence of paraffinembedded tissue, unstained paraffin-embedded tumor slides are acceptable).
- •Measurable disease, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines
- •HER2 negative tumors. HER2 negativity must be confirmed by one of the following:
- •FISH-negative (FISH ratio \<2.2), or
- •IHC 0-1+, or
- •IHC 2-3+ AND FISH-negative (FISH ratio \<2.2)
Exclusion Criteria
- •Patients with brain metastases are not eligible.
- •History of another primary cancer, with the exception of the following:
- •Curatively treated in situ cervical cancer;
- •Curatively resected non-melanoma skin cancer;
- •Other primary solid tumor curatively treated with no known active disease present and no treatment administered for \>=5 years prior to study enrollment.
- •History of interstitial lung disease (e.g., pneumonitis, pulmonary fibrosis), or any evidence of interstitial lung disease on the CT scan of the chest performed at the baseline visit.
- •Prior anti-EGFR antibody therapy (e.g., cetuximab), or treatment with small-molecule EGFR inhibitors (e.g., gefitinib, erlotinib, lapatinib).
- •Radiotherapy \<=14 days prior to study enrollment. Any acute effects of radiotherapy must be resolved prior to the administration of study drugs.
- •Systemic chemotherapy, hormonal therapy, immunotherapy, or experimental or approved proteins/antibodies (e.g., bevacizumab) \<=21 days prior to study enrollment.
- •Prior therapy with gemcitabine or carboplatin in the metastatic setting is not permitted. Patients who received gemcitabine or carboplatin as part of adjuvant therapy are eligible, as long as recurrence was first documented \>12 months after the last exposure to the drug(s).
Arms & Interventions
Panitumumab/Gemcitabine/Carboplatin
Systemic therapy
Intervention: Panitumumab
Panitumumab/Gemcitabine/Carboplatin
Systemic therapy
Intervention: Carboplatin
Panitumumab/Gemcitabine/Carboplatin
Systemic therapy
Intervention: Gemcitabine
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: every 6 weeks until treatment discontinuation
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
Secondary Outcomes
- Objective Response Rate and Clinical Benefit Rate(every 6 weeks until treatment discontinuation)
- Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity(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(18 months)