Pembrolizumab, Letrozole, and Palbociclib in Treating Patients With Stage IV Estrogen Receptor Positive Breast Cancer With Stable Disease That Has Not Responded to Letrozole and Palbociclib
|Estrogen Receptor Positive HER2/Neu Negative Postmenopausal Recurrent Breast Carcinoma Stage IV Breast Cancer||Other: Laboratory Biomarker Analysis Drug: Letrozole Drug: Palbociclib Biological: Pembrolizumab||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase II Study of the Addition of MK-3475 (Pembrolizumab) to Letrozole and Palbociclib in Patients With Metastatic Estrogen Receptor Positive Breast Cancer Who Have Stable Disease But Are Not Responding to Letrozole and Palbociclib|
- Response rate (CR or PR) assessed using RECIST version 1.1 [ Time Frame: Up to 24 months ]
- Clinical Benefit Response assessed using RECIST version 1.1 [ Time Frame: Up to 24 months ]
- Duration Of Response assessed using RECIST version 1.1 [ Time Frame: Up to 24 months ]
- Incidence of adverse events assessed by NCI CTCAE, version 4 [ Time Frame: Up to 24 months ]Adverse events will be analyzed including but not limited to all AEs, SAEs, fatal AEs, and laboratory changes. Immune-related adverse events will also be collected.
- Overall Survival assessed using RECIST version 1.1 [ Time Frame: Up to 24 months ]Generated using Kaplan-Meier estimates.
- Progression Free Survival assessed using RECIST version 1.1 [ Time Frame: Up to 24 months ]Generated using Kaplan-Meier estimates.
- Time to treatment failure assessed using irRECIST [ Time Frame: Up to 24 months ]Generated using Kaplan-Meier estimates
- Clinical benefit assessed using irRECIST [ Time Frame: Up to 24 months ]
- Tumor response assessed using irRECIST [ Time Frame: Up to 24 months ]
|Actual Study Start Date:||September 30, 2016|
|Estimated Study Completion Date:||September 2018|
|Estimated Primary Completion Date:||September 2018 (Final data collection date for primary outcome measure)|
Experimental: Treatment (letrozole, palbociclib, pembrolizumab)
Patients receive letrozole PO QD on days 1-28 and palbociclib PO QD for 3 weeks. Courses with letrozole and palbociclib repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes on day 1. Courses with pembrolizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Letrozole
Other Names:Drug: Palbociclib
Other Names:Biological: Pembrolizumab
I. To evaluate the objective response rate (ORR), based on Response Evaluation Criteria In Solid Tumors [RECIST], version 1.1), of pembrolizumab in combination with letrozole and palbociclib in patients with metastatic estrogen receptor (ER)+human epidermal growth factor receptor (HER)2- breast cancer, and determine if the addition of pembrolizumab in patients with stable disease (SD) on letrozole and palbociclib can achieve a response (complete response [CR], partial response [PR], and ORR) measured from the study baseline, based on RECIST version 1.1.
I. To determine the safety and tolerability of adding pembrolizumab (200 mg every 3 weeks) to ongoing treatment with letrozole (2.5 mg) and palbociclib (3 weeks on, one week off: dose of palbociclib can vary secondary to individual patient tolerance, range 75-125 mg) in patients with metastatic ER+HER2- breast cancer.
II. To evaluate progression-free survival (PFS). III. To evaluate overall survival (OS). IV. To evaluate duration of response (DOR) using RECIST version 1.1. V. To evaluate clinical benefit rate (CBR) using RECIST version 1.1. VI. To evaluate toxicities (using the National Cancer Institute [NCI] Common Terminology Criteria for adverse Events [CTCAE], version 4.0) associated with the triple drug combination (pembrolizumab, letrozole, and palbociclib) in patients with metastatic ER+HER2- breast cancer.
VII. To evaluate CR, PR, ORR, PFS, DOR, and CBR using immune-related Response Criteria In Solid Tumors (irRECIST); time to treatment failure will also be assessed.
I. To study cellular/humoral immune response by analyzing immune and stromal cell characteristics before and after treatment that correlate with clinical response; this includes programmed cell death 1 ligand 1 (PD-L1) expression levels.
II. To study the peripheral serum thymidine kinase (TK) level and its association with treatment response.
III. To study circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and the effect of combining pembrolizumab, letrozole, and palbociclib on ctDNA profiles.
Patients receive letrozole orally (PO) once daily (QD) on days 1-28 and palbociclib PO QD for 3 weeks. Courses with letrozole and palbociclib repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses with pembrolizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days, every 6 months for 3 years, and then every 12 months for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02778685
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Yuan Yuan, MD, PhD 800-826-4673|
|Principal Investigator: Yuan Yuan, MD, PhD|
|City of Hope Antelope Valley||Recruiting|
|Lancaster, California, United States, 93534|
|Contact: Suzanne Branch 626-256-4673 ext 25648|
|Sub-Investigator: Nimit Sudan, MD|
|City of Hope Rancho Cucamonga||Recruiting|
|Rancho Cucamonga, California, United States, 91730|
|Contact: Valerie Estala 626-256-4673 ext 81699|
|Sub-Investigator: Benham Ebrahimi, MD|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Odessa Rodriguez 626-256-4673 ext 81409|
|Sub-Investigator: Christina Yeon, MD|
|City of Hope West Covina||Recruiting|
|West Covina, California, United States, 91790|
|Contact: Mei Zheng 626-256-4673 ext 81336|
|Sub-Investigator: Gargi Upadhyaya, MD|
|Principal Investigator:||Yuan Yuan, MD, PhD||City of Hope Medical Center|