A Pilot and Phase II Study to Assess the Safety, Tolerability and Efficacy of Pembrolizumab Plus Chemotherapy in Metastatic Triple Negative Breast Cancer Patients
Overview
- Phase
- Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- Providence Health & Services
- Enrollment
- 29
- Locations
- 4
- Primary Endpoint
- Treatment-Associated Adverse Events Requiring Discontinuation
- Status
- Active, not recruiting
- Last Updated
- 8 days ago
Overview
Brief Summary
The goal of this study is to establish the safety and tolerability of pembrolizumab when administered in combination with either of two chemotherapy regimens (weekly paclitaxel or capecitabine) in unresectable/metastatic triple negative breast cancer (MTNBC) patients.
Detailed Description
In the pilot phase, patients will be enrolled to one of two experimental arms, which will be selected by the treating investigator (arm A: pembrolizumab + weekly paclitaxel; arm B: pembrolizumab + capecitabine). Subjects will receive pembrolizumab via intravenous (IV) infusion at 200mg every three weeks (Q3W), and continue treatment Q3W until progression of disease, initiation of alternative cancer therapy, unacceptable toxicity, or other reasons to discontinue treatment occur, up to 24 months. Paclitaxel will be administered intervenously on a weekly schedule at a dose of 80mg/m2. Oral capecitabine will be administered at total daily dose of 4,000 mg (2,000 mg two times each day (abbreviated BID)). Capecitabine will be administered as intermittent therapy given on days 1-7 in 14-day cycles.
Investigators
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.
- •HER2-negative breast cancer (defined by immunohistochemistry (IHC) 0-1 (or) IHC 2 and in situ hybridization (ISH) HER2 / centromere on chromosome 17 (CEP17) \< 2.0);
- •ER and PR-negative breast cancer (defined by IHC\<1%);
- •Measurable metastatic or unresectable disease based on response evaluation criteria in solid tumours (RECIST) 1.
- •Indicated for treatment with either weekly paclitaxel or oral capecitabine, as first or second-line chemotherapy in the metastatic/unresectable setting (as determined by the consenting investigator);
- •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 during screening. Archival tissue is acceptable if no intervening anti-neoplastic therapy has been administered, and if sufficient material is available for analysis (see section 8.0 for requirements);
- •Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- •Demonstrate adequate organ function as defined by protocol defined lab values
- •Female subjects of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
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 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 TB (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. Denosumab is allowed.
- •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 and alopecia are an exception to this criterion and may qualify for the study.
- •Has received the assigned chemotherapy regimen previously in the metastatic setting, or has received the assigned chemotherapy regimen previously in the (neo)adjuvant setting within 12 months of consent;
- •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 progressed or required active treatment in the last 5 years.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
Arms & Interventions
Arm A
pembrolizumab + weekly paclitaxel
Intervention: Pembrolizumab
Arm A
pembrolizumab + weekly paclitaxel
Intervention: Paclitaxel
Arm B
pembrolizumab + capecitabine
Intervention: Pembrolizumab
Arm B
pembrolizumab + capecitabine
Intervention: Capecitabine
Outcomes
Primary Outcomes
Treatment-Associated Adverse Events Requiring Discontinuation
Time Frame: 6 weeks
The count of participants who experienced serious adverse events and grade III/IV treatment-associated adverse events requiring discontinuation of pembrolizumab.
Number of Patients Who Complete Chemotherapy Without a Dose Delay of More Than 21 Days.
Time Frame: 6 weeks
The number of patients who complete 6 weeks of chemotherapy without requiring a dose delay of more than 21 days.
Secondary Outcomes
- Overall Response Rate(12 weeks)