A Phase II Study of Pembrolizumab Plus Carboplatin in BRCA-related Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab 25 MG(milligram)/ML
- Conditions
- Metastatic Breast Cancer
- Sponsor
- CORTESI LAURA
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- The ORR
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a prospective two-stage single arm phase II study to be conducted in conformance with Good Clinical Practices.
This study will enrol 53 patients, based on a two steps Simon's design.
Patients will entry into the study if the following conditions will be satisfied:
- BRCA1/2 germline mutations.
- Metastatic disease with measurable lesions will be evaluated by computed tomography or by PET (Positron Emission Tomography) scan.
- Patients must have received anthracycline and taxanes before entry into the study.
Patients will be treated with Carboplatin AUC6 (Area Under The Curve) EV (endovenous) every 3 weeks in combination with Pembrolizumab 200 mg EV every 3 weeks for 6 cycles. Afterwards, the Pembrolizumab will recontinued with the same schedule until unacceptable toxicity or disease progression.
The primary endpoint will be Objective Responses Rate (ORR) (complete answers + partial answers) evaluated according to the RECIST criteria.
Investigators
CORTESI LAURA
Principal Investigator
Azienda Ospedaliero-Universitaria di Modena
Eligibility Criteria
Inclusion Criteria
- •Be willing and able to provide written informed consent/assent for the trial.
- •Be 18 years of age on day of signing informed consent.
- •Patients must have metastatic confirmed breast cancer
- •Disease progression by radiological techniques within 12 months prior to signing informed consent
- •Documented mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (unknown significance variants)
- •Have measurable disease based on RECIST 1.
- •Prior chemotherapy with anthracyclines and taxanes has to be administered in neoadjuvant or adjuvant setting.
- •Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day
- •Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
Exclusion Criteria
- •Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
- •Has a benign variant of BRCA1/2 genes
- •Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- •Has a known history of active Bacillus Tuberculosis
- •Hypersensitivity to pembrolizumab or any of its excipients.
- •Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
- •Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- •Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- •Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Arms & Interventions
single arm
Carboplatin AUC6 EV will be given every 3 weeks in combination with Pembrolizumab 200 mg EV every 3 weeks for 6 cycles. Afterwards, the Pembrolizumab will come continued with the same schedule until unacceptable toxicity or disease progression
Intervention: Pembrolizumab 25 MG(milligram)/ML
Outcomes
Primary Outcomes
The ORR
Time Frame: through study completion, an average of 1 year
objective response rate (complete response plus partial response) will be evaluated according to RECIST criteria
Secondary Outcomes
- TTP (time to tumor progression)(through study completion, an average of 1 year)