Pilot Study of Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Metastatic Triple Negative Breast Cancer
- Sponsor
- Case Comprehensive Cancer Center
- Enrollment
- 30
- Locations
- 2
- Primary Endpoint
- Overall Response Rate (ORR) in Patients Treated With CNP
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to see how effective the combination of the two chemotherapy drugs (carboplatin and nab-paclitaxel) are when added to a third drug, pembrolizumab.
Pembrolizumab is an investigational (experimental) drug that works by reinvigorating the immune system, allowing it to target and destroy cancer cells. Pembrolizumab is experimental because it is not approved by the Food and Drug Administration (FDA) for this type of breast cancer treatment.
Detailed Description
Primary Objective - Determine overall response rate (ORR) in patients treated with CNP Secondary Objective(s) * Determine progression-free survival (PFS), and disease control rate (DCR) in patients treated with CNP. * Determine duration of response in patients treated with CNP. * Determine safety/tolerability of CNP. Correlative Endpoints - Identify pathologic and genomic correlates of response to CNP. Study design including dose escalation / cohorts This is prospective pilot clinical trial of CNP in up to 30 patients with mTNBC
Investigators
Joseph Baar, MD, PhD
Associate Professor of Medicine
Case Comprehensive Cancer Center
Eligibility Criteria
Inclusion Criteria
- •Subjects must have histologically or cytologically confirmed metastatic triple negative breast cancer
- •Subjects must have received no more than 2 prior therapies for this disease
- •ECOG Performance Status 0-1
- •Subjects must have normal organ and marrow function as defined below:
- •Hemoglobin ≥ 10.0 g/dl
- •Absolute neutrophil count ≥ 1,000/μL
- •Platelet count ≥ 100,000/μL
- •Total bilirubin within normal institutional limits
- •AST (SGOT) ≤ 2.5 X institutional upper limit of normal
- •ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
Exclusion Criteria
- •Prior treatment toxicities have not resolved to ≤ Grade 1 according to NCI CTCAE Version 4.0 (except for alopecia and neuropathy)
- •Subjects receiving any other investigational agents
- •Subjects with radiographically stable treated brain metastases are eligible but must not have been on steroid therapy for at least 4 weeks
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, carboplatin, pembrolizumab, or other agents used in this study
- •Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or breastfeeding women are excluded from this study
- •Patients with conditions requiring immunosuppressive medications or chronic infections (including HIV infection, hepatitis B and C)
- •Patients with chronic autoimmune disease
- •Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1)
- •Patients with evidence of active, non-infectious pneumonia
Arms & Interventions
Carboplatin + Nab-paclitaxel + Pembrolizumab
Combination therapy of Carboplatin, Nab-paclitaxel, and Pembrolizumab
Intervention: Carboplatin
Carboplatin + Nab-paclitaxel + Pembrolizumab
Combination therapy of Carboplatin, Nab-paclitaxel, and Pembrolizumab
Intervention: Nab-paclitaxel
Carboplatin + Nab-paclitaxel + Pembrolizumab
Combination therapy of Carboplatin, Nab-paclitaxel, and Pembrolizumab
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Overall Response Rate (ORR) in Patients Treated With CNP
Time Frame: Up to 24 months
The number of people with tumor responses according to RECIST (V1.1). These responses include Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Secondary Outcomes
- Progression-free Survival (PFS) in Patients Treated With CNP(Up to 24 months)
- Disease Control Rate (DCR) in Patients Treated With CNP(Up to 24 months)
- Duration of Response in Patients Treated With CNP(Up to 24 months)