Pembrolizumab, Letrozole, and Palbociclib in Treating Postmenopausal Patients With Newly Diagnosed Metastatic Stage IV Estrogen Receptor Positive Breast Cancer
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ClinicalTrials.gov Identifier: NCT02778685 |
Recruitment Status :
Recruiting
First Posted : May 20, 2016
Last Update Posted : February 12, 2021
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Tracking Information | |||||
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First Submitted Date ICMJE | May 18, 2016 | ||||
First Posted Date ICMJE | May 20, 2016 | ||||
Last Update Posted Date | February 12, 2021 | ||||
Actual Study Start Date ICMJE | February 14, 2017 | ||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Response rate (CR or PR) assessed using RECIST version 1.1 [ Time Frame: Up to 24 months ] | ||||
Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures |
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Original Other Pre-specified Outcome Measures | Same as current | ||||
Descriptive Information | |||||
Brief Title ICMJE | Pembrolizumab, Letrozole, and Palbociclib in Treating Postmenopausal Patients With Newly Diagnosed Metastatic Stage IV Estrogen Receptor Positive Breast Cancer | ||||
Official Title ICMJE | Phase II Study of the Combination of Pembrolizumab, Letrozole and Palbociclib in Postmenopausal Patients With Newly Diagnosed Metastatic Estrogen Receptor Positive Breast Cancer | ||||
Brief Summary | This phase II trial studies how well pembrolizumab works when given together with letrozole and palbociclib in treating postmenopausal patients with newly diagnosed stage IV estrogen receptor positive breast cancer that has spread to other parts of the body (metastatic). 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. Estrogen can cause the growth of breast cancer cells. Antihormone therapy, such as letrozole, may lessen the amount of estrogen made by the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab, letrozole, and palbociclib may be an effective treatment for patients with stage IV estrogen receptor positive breast cancer. | ||||
Detailed Description | PRIMARY OBJECTIVES: 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 newly diagnosed metastatic estrogen receptor (ER)+human epidermal growth factor receptor (HER)2- breast cancer, and determine if the addition of pembrolizumab to letrozole and palbociclib combination can achieve an improved response rate (ORR = complete response [CR] + partial response [PR]) measured from the study baseline, based on RECIST version 1.1. SECONDARY OBJECTIVES: I. To determine the safety and tolerability of adding pembrolizumab (200 mg every 3 weeks) to letrozole (2.5 mg) and palbociclib (125 mg 3 weeks on, one week off) in patients with metastatic ER+HER2- breast cancer. II. To evaluate the CR rate. III. To evaluate progression-free survival (PFS). IV. To evaluate overall survival (OS). V. To evaluate duration of response (DOR) using RECIST version 1.1. VI. To evaluate clinical benefit rate (CBR) using RECIST version 1.1. VII. 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. VIII. 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. TERTIARY OBJECTIVES: 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. IV. To evaluate genomic and phenotypic status of breast tumor. OUTLINE: Patients receive letrozole orally (PO) once daily (QD) on days 1-28 and palbociclib PO QD for 3 weeks. Cycless 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. Cycles 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. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE | Experimental: Treatment (letrozole, palbociclib, pembrolizumab)
Patients receive letrozole PO QD on days 1-28 and palbociclib PO QD for 3 weeks. Cycles 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. Cycles with pembrolizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Interventions:
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Publications * | Egelston C, Guo W, Yost S, Lee JS, Rose D, Avalos C, Ye J, Frankel P, Schmolze D, Waisman J, Lee P, Yuan Y. Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. J Immunother Cancer. 2021 Mar;9(3). pii: e002084. doi: 10.1136/jitc-2020-002084. | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
22 | ||||
Original Estimated Enrollment ICMJE |
18 | ||||
Estimated Study Completion Date ICMJE | December 31, 2021 | ||||
Estimated Primary Completion Date | December 31, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE | |||||
Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT02778685 | ||||
Other Study ID Numbers ICMJE | 16058 NCI-2016-00694 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 16058 ( Other Identifier: City of Hope Medical Center ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | City of Hope Medical Center | ||||
Study Sponsor ICMJE | City of Hope Medical Center | ||||
Collaborators ICMJE | National Cancer Institute (NCI) | ||||
Investigators ICMJE |
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PRS Account | City of Hope Medical Center | ||||
Verification Date | February 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |