A Phase II Study of Anti-PD-1 (Pembrolizumab) in Combination With Hormonal Therapy During or After Radiation in Patients With Hormone Receptor (HR)-Positive Localized Inflammatory Breast Cancer (IBC) Who Did Not Achieve a Pathological Complete Response (pCR) to Neoadjuvant Chemotherapy
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Anatomic Stage IIIB Breast Cancer AJCC v8
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Disease free survival (DFS)
- Status
- Active, not recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
This phase II trial studies how well pembrolizumab works in treating patients with hormone receptor positive inflammatory breast cancer that has not spread to other parts of the body, who are receiving hormone therapy and did not achieve a pathological complete response to chemotherapy. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the disease free survival (DFS) at 2 years of patients with maintenance therapy using pembrolizumab in combination with standard adjuvant hormonal therapy. II. To determine the safety and toxicity profile of primary inflammatory breast cancer (IBC) patients who received combination of pembrolizumab and hormone receptor blockade. EXPLORATORY OBJECTIVES: I. To investigate the association between immune related biomarkers in the peripheral blood and tumor tissue, such as PD-L1 expression, with safety and efficacy for IBC patients treated with pembrolizumab. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 1 and 24 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is willing and able to provide written informed consent for the trial.
- •Is a female or male and \>/= 18 years of age
- •Has histological confirmation of breast carcinoma.
- •Has confirmed inflammatory breast cancer by using international consensus criteria:
- •Onset: Rapid onset of breast erythema, edema and/or peau d'orange, and/or warm breast, with/without an underlying breast mass
- •Duration: History of such findings no more than 6 months
- •Extent: Erythema occupying at least 1/3 of whole breast
- •Pathology: Pathologic confirmation of invasive carcinoma
- •Did not achieve pathological complete response (pCR) to any chemotherapy that was given with the intention to induce best response prior surgery. pCR is defined as the current American Joint Committee on Cancer (AJCC) breast cancer staging.
- •Is HER2 normal, defined as HER2 0 or 1+ by IHC and negative by FISH if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed.
Exclusion Criteria
- •Is currently participating in a study of an investigational anti-cancer agent.
- •Has a diagnosis of immunodeficiency or any other form of immunosuppressive therapy.
- •Has not recovered from adverse events due to prior therapies, i.e. monoclonal antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or surgery.
- •\- Note: Participants with ≤ Grade 2 neuropathy, alopecia and general disorders and administration site conditions (per CTCAE version 4.0) are an exception to this criterion and may qualify for the study.
- •Has a known history of prior malignancy with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, and has undergone potentially curative therapy and has no evidence of recurrence over the last 1 year since completion of curative therapy.
- •Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or immunosuppressive agents. Participants with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Participants that require intermittent use of bronchodilators, inhaled steroid or local steroid injections to the skin would not be excluded from the study. Participants with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.
- •Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- •Has an active infection requiring systemic therapy.
- •Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
Arms & Interventions
Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Disease free survival (DFS)
Time Frame: Up to 24 months
Will be summarized with a corresponding 95% confidence interval. DFS will be compared with the historical control rate of 60% at year two by using a one-sided exponential MLE test. Cox proportional hazards regression analysis will be used to model the association between DFS and disease and demographic covariates of interest, including immune-related biomarkers in the peripheral blood and tumor tissue.
Secondary Outcomes
- Incidence of adverse events(Up to 1 month after last pembrolizumab dose)
- Overall survival (OS)(From the start of the study up to 24 months)