Open-label, Single Center, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab in Combination With Carboplatin and Paclitaxel in Patients With Stage 1 cT1b-T1cN0M0 Triple Negative Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Stage 1 cT1b-T1cN0M0
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Safety and adverse events (AEs)
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
To look at the effectiveness of the combination of pembrolizumab, carboplatin, and paclitaxel in participants with stage 1 cT1b-T1cN0M0 Triple Negative Breast Cancer.
Detailed Description
Primary Objective To estimate the rate of pCR in patients with cT1b and T1cN0M0 TNBC after neoadjuvant therapy with 4 cycles of Pembrolizumab + Carboplatin + Paclitaxel. Secondary Objective To assess the safety and toxicity profile of pembrolizumab plus chemotherapy in participants receiving an anthracycline-de-escalated regimen of carboplatin, paclitaxel and pembrolizumab by recording the incidence of treatment emergent adverse events. Exploratory Objectives 1. To estimate the invasive disease-free survival (iDFS), and overall survival (OS) in participants with cT1b-T1cN0 TNBC that receive neoadjuvant pembrolizumab plus chemotherapy in the setting of an anthracycline de-escalation study. 2. To explore if there is a molecular signature associated with response or lack of response to therapy. 3. To evaluate patient reported outcomes of participants receiving this de-escalated regimen.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Participants must have histologically confirmed ER negative, PR negative and HER2-negative (TNBC) defined as ER\<10%, PR\<10%, and HER2 negative (per 2018 ASCO CAP guidelines). All pathology will be confirmed at the MD Anderson Houston Campus. Participants with tumors designated as HER2 equivocal (per ASCO CAP guidelines) are eligible if in view of treating physician patient is not considered a candidate for HER2-targeted therapy. Participants with weakly ER or PR positive disease, defined as ER and/or PR between 1-9% by immunohistochemistry, are eligible if the treating physician considers the participants not eligible for adjuvant endocrine therapy.
- •AJCC 8 anatomic tumor Stage 1 T1b-T1c, N0, M
- •All participants with clinically suspicious nodes must undergo core or fine needle biopsy per standard clinical practice to pathologically assess at least 1 suspicious index node. Participants with suspicious nodes that are biopsy negative will be eligible.
- •Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of Stage 1 T1b-T1cN0M0 TNBC will be enrolled in this study.
- •Male participants: A male participant must agree to use a contraception as detailed in Appendix 2 of this protocol during the treatment period and for at least 120 days, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and/or any active comparator/combination) plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose after the last dose of study treatment and refrain from donating sperm during this period.
- •Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 2), not breastfeeding, and at least one of the following conditions applies:
- •Not a woman of childbearing potential (WOCBP) as defined in Appendix 2 OR
- •A WOCBP who agrees to follow the contraceptive guidance in Appendix 2 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatment(s) (pembrolizumab and/or any active comparator/combination) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.
- •Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.
Exclusion Criteria
- •Participants are excluded from the study if any of the following criteria apply:
- •Stage 2, 3 or 4 Triple negative breast cancer
- •Hormone Receptor positive and/or Human Epidermal Growth factor 2 (HER 2) positive breast cancer
- •A WOCBP who has a positive urine pregnancy test within 72 hours prior to dose of study drug (see Appendix 2). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks to allocation of therapy.
- •Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
- •Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
- •Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Arms & Interventions
Pathologic Complete Response
If a participant's tissue shows a pathological complete response to treatment, participants will receive up to 13 cycles of pembrolizumab alone. Pathological complete response means that the study team cannot find any evidence of cancer in the breast or lymph node tissue sample that was removed during the participants surgery, after the participant completes the 4 cycles of carboplatin, pembrolizumab and paclitaxel.
Intervention: Carboplatin
Pathologic Complete Response
If a participant's tissue shows a pathological complete response to treatment, participants will receive up to 13 cycles of pembrolizumab alone. Pathological complete response means that the study team cannot find any evidence of cancer in the breast or lymph node tissue sample that was removed during the participants surgery, after the participant completes the 4 cycles of carboplatin, pembrolizumab and paclitaxel.
Intervention: Paclitaxel
Pathologic Complete Response
If a participant's tissue shows a pathological complete response to treatment, participants will receive up to 13 cycles of pembrolizumab alone. Pathological complete response means that the study team cannot find any evidence of cancer in the breast or lymph node tissue sample that was removed during the participants surgery, after the participant completes the 4 cycles of carboplatin, pembrolizumab and paclitaxel.
Intervention: Pembrolizumab
Non-Pathologic Complete Response
If a participant's tissue does not show a pathological complete response, the participant will receive 4 cycles of pembrolizumab plus 2 other drugs (doxorubicin and cyclophosphamide), followed by 9 cycles of pembrolizumab alone.
Intervention: Carboplatin
Non-Pathologic Complete Response
If a participant's tissue does not show a pathological complete response, the participant will receive 4 cycles of pembrolizumab plus 2 other drugs (doxorubicin and cyclophosphamide), followed by 9 cycles of pembrolizumab alone.
Intervention: Paclitaxel
Non-Pathologic Complete Response
If a participant's tissue does not show a pathological complete response, the participant will receive 4 cycles of pembrolizumab plus 2 other drugs (doxorubicin and cyclophosphamide), followed by 9 cycles of pembrolizumab alone.
Intervention: Pembrolizumab
Non-Pathologic Complete Response
If a participant's tissue does not show a pathological complete response, the participant will receive 4 cycles of pembrolizumab plus 2 other drugs (doxorubicin and cyclophosphamide), followed by 9 cycles of pembrolizumab alone.
Intervention: Doxorubicin
Non-Pathologic Complete Response
If a participant's tissue does not show a pathological complete response, the participant will receive 4 cycles of pembrolizumab plus 2 other drugs (doxorubicin and cyclophosphamide), followed by 9 cycles of pembrolizumab alone.
Intervention: Cyclophosphamide
Outcomes
Primary Outcomes
Safety and adverse events (AEs)
Time Frame: Through study completion; an average of 1 year.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0