Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02971761|
Recruitment Status : Recruiting
First Posted : November 23, 2016
Last Update Posted : November 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Androgen Receptor Positive Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor Negative Recurrent Breast Carcinoma Stage III Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Metastatic Triple-Negative Breast Carcinoma||Drug: Enobosarm Other: Laboratory Biomarker Analysis Biological: Pembrolizumab||Phase 2|
I. To evaluate the safety/tolerability of the combination regimen.
II. To determine the response rate (complete response [CR] or partial response [PR] via Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) of the combination of pembrolizumab with enobosarm (GTx-024) in patients with advanced androgen receptor (AR) positive (+) triple negative breast cancer (TNBC).
I. To evaluate clinical outcomes by RECIST 1.1 including clinical benefit rate (CBR) at 24 weeks, progression free-survival (PFS), duration of response (DOR), event free survival (EFS), time-to-treatment failure (TTF); and overall survival (OS).
II. To evaluate the role of immune-related response criteria (irRECIST).
III. To evaluate the association of AR by immunohistochemistry (IHC) and clinical response.
I. To evaluate the association of an AR gene expression signature and clinical response.
II. To evaluate genomic and phenotypic status of breast tumor.
III. To evaluate the effect of the combination therapy on peripheral blood circulating tumor cells (CTCs) and circulating tumor deoxyribonucleic acid (DNA) (ctDNA).
IV. To evaluate the effect of combination therapy on tumor-derived exosomes (TEX) and TEX associated immune biomarkers.
V. To evaluate pre-treatment programmed death ligand 1 (PD-L1) and tumor infiltrating lymphocytes (TILs) as a predictor of response to combination therapy.
VI. To evaluate specific TIL subsets (e.g. CD4, CD8, regulatory T cell [Treg] distribution) and other immunological correlative (e.g. T cell receptor [TCR] repertoire analysis) as possible predictors of response.
VII. To evaluate change in TILs as a result of the combination therapy.
VIII. To evaluate peripheral blood, immune biomarkers.
OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and enobosarm orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 and 90 days, every 3 months, and bi-annually.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Clinical Trial of the Combination of Pembrolizumab and Selective Androgen Receptor Modulator (SARM) GTX-024 in Patients With Metastatic Androgen Receptor (AR) Positive Triple Negative Breast Cancer (TNBC)|
|Actual Study Start Date :||June 1, 2017|
|Estimated Primary Completion Date :||October 2019|
|Estimated Study Completion Date :||October 2019|
Experimental: Treatment (pembrolizumab, enobosarm)
Patients receive pembrolizumab IV over 30 minutes on day 1 and enobosarm PO QD on days 1-21. Courses repeat every 21 days for up to 35 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
- Dose limiting toxicities assessed by NCI CTCAE v4.0 [ Time Frame: Up to 21 days ]
- Incidence of adverse events (AEs) assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [ Time Frame: Up to 36 months ]AEs will be analyzed including but not limited to all AEs, serious adverse events, fatal AEs and laboratory changes. Immune-related adverse events will also be collected.
- Response rate (CR or PR) assessed using RECIST v1.1 [ Time Frame: Up to 36 months ]
- CBR assessed by irRECIST [ Time Frame: 24 weeks ]
- DOR defined as time from documentation of tumor response to disease progression or death in CR or PR patients assessed by irRECIST [ Time Frame: Up to 36 months ]
- EFS defined as failure of treatment or death as a result of any cause assessed by RECIST v1.1 [ Time Frame: Up to 1 year ]Kaplan-Meier estimates will be generated.
- OS assessed by RECIST v1.1 [ Time Frame: Time to death as a result of any cause, assessed up to 36 months ]Kaplan-Meier estimates will be generated.
- PFS assessed using RECIST v1.1 [ Time Frame: Time to disease progression/relapse or death as a result of any cause, assessed up to 36 months ]Kaplan-Meier estimates will be generated.
- TTF defined as time to treatment termination for any reason assessed by RECIST v1.1 [ Time Frame: Up to 36 months ]
- AR expression profile assessed in tumor by IHC [ Time Frame: Up to 36 months ]
- miRNA/mRNA profiling assessed in tumor and blood [ Time Frame: Up to 36 months ]
- Number of CTCS and quantitation of ctDNA assessed in blood [ Time Frame: Up to 36 months ]
- PD-L1 and TIL profile, immune signatures, and genomic analysis assessed in tumor [ Time Frame: Up to 36 months ]
- Temporal profile of tumor-derived exosomes assessed in peripheral blood [ Time Frame: Up to 36 months ]
- Temporal profile of TIL subsets and other immunological correlatives assessed in tumor and blood [ Time Frame: Up to 36 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02971761
|United States, California|
|City of Hope Corona||Recruiting|
|Corona, California, United States, 92879|
|Contact: Cheryl Corpus 626-256-4673 ext 81529 email@example.com|
|Principal Investigator: Misagh Karimi, MD|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Yuan Yuan, MD, PhD 626-256-4673 ext 89200 firstname.lastname@example.org|
|Principal Investigator: Yuan Yuan, MD, Phd|
|City of Hope Antelope Valley||Recruiting|
|Lancaster, California, United States, 93534|
|Contact: Regan Johnson 626-256-4673 ext 25648 email@example.com|
|Principal Investigator: Mohammad Fekrazad, MD|
|City of Hope Mission Hills||Recruiting|
|Mission Hills, California, United States, 91345|
|Contact: Amy Shousha 626-256-4673 ext 81865 firstname.lastname@example.org|
|Principal Investigator: Suzy Melkonian, MD|
|City of Hope Rancho Cucamonga||Recruiting|
|Rancho Cucamonga, California, United States, 91730|
|Contact: Valerie Estala 626-256-4673 ext 81699 email@example.com|
|Principal Investigator: Benham Ebrahimi, MD|
|University of California Davis Comprehensive Cancer Center||Not yet recruiting|
|Sacramento, California, United States, 95817|
|Contact: Mili Arora, MD 916-734-8614 firstname.lastname@example.org|
|Principal Investigator: Mili Arora, MD|
|City of Hope South Pasadena||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Odessa T. Rodriguez 626-256-4673 ext 81409 email@example.com|
|Principal Investigator: Christina H. Yeon|
|City of Hope West Covina||Recruiting|
|West Covina, California, United States, 91790|
|Contact: Mei Zheng 626-256-4673 ext 81336 firstname.lastname@example.org|
|Principal Investigator: Gargi Upadhyaya, MD|
|United States, Kansas|
|University of Kansas Cancer Center||Not yet recruiting|
|Kansas City, Kansas, United States, 66160|
|Contact: Anne O'Dea, MD 913-588-7750 email@example.com|
|Principal Investigator: Anne O'Dea, MD|
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center||Not yet recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Daniel Stover, MD 614-685-6700 Daniel.Stover@osumc.edu|
|Principal Investigator: Daniel Stover, MD|
|United States, Utah|
|Huntsman Cancer Institute/University of Utah||Not yet recruiting|
|Salt Lake City, Utah, United States, 84112|
|Contact: Adam Cohen, MD 801-587-4725 firstname.lastname@example.org|
|Principal Investigator: Adam Cohen, MD|
|Principal Investigator:||Yuan Yuan, MD, PhD||City of Hope Medical Center|