Pembrolizumab and Tamoxifen With or Without Vorinostat for the Treatment of Estrogen Receptor Positive Breast Cancer

NCT04190056 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 197520NCI-2019-07572
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab and tamoxifen with or without vorinostat work for the treatment of estrogen receptor positive breast cancer. 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. Hormone therapy with tamoxifen may may fight breast cancer by blocking the use of estrogen by the tumor cells. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial is being done to find a drug combination to better control estrogen receptor positive breast cancer and reduce the number of pills taken.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Prognostic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the proportion of participants randomized to that arm whose status is stable disease (SD) or better (complete response (CR), partial response (PR)). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: CR=Disappearance of all target lesions; PR = \>=30% decrease in the sum of the longest diameter of target lesions, and SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease,.

  Up to 24 weeks

Secondary Outcomes (4)

• Percentage of Participants With Tumor Responses

  Up to 24 months

• Duration of Response (DOR)

  Up to 24 weeks

• Median Progression Free Survival (PFS)

  Up to 27 months

• Median Overall Survival (OS)

  Up to 27 months

Study Arms (2)

Arm A (pembrolizumab, vorinostat, tamoxifen)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1, vorinostat PO QD for 4 days weekly, and tamoxifen PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity.

Biological: Pembrolizumab; Drug: Tamoxifen; Drug: Vorinostat

Arm B (pembrolizumab, tamoxifen)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1 and tamoxifen PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression of unacceptable toxicity.

Biological: Pembrolizumab; Drug: Tamoxifen

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Arm A (pembrolizumab, vorinostat, tamoxifen); Arm B (pembrolizumab, tamoxifen)

Tamoxifen DRUG

Given PO

Arm A (pembrolizumab, vorinostat, tamoxifen); Arm B (pembrolizumab, tamoxifen)

Vorinostat DRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Arm A (pembrolizumab, vorinostat, tamoxifen)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre and postmenopausal women or men with stage IV ER+ breast cancer histological or cytological confirmation
• \> 10% expression of PD-1/Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) dual staining in Cluster of differentiation 8 (CD8) cells in tumor or blood or \>5% expression of PD-1/CTLA-4 dual staining in CD4 in blood (only).
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 1
• Understand and voluntarily sign an informed consent prior to any study-related assessments or procedures are conducted and are able to adhere to the study visit schedule and other protocol requirements
• Consent to paired tumor biopsy
• Measurable tumor by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Per Good Clinical Practice, any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with anti-PD1 therapy should be resolved to less than grade 1
• Absolute neutrophil count (ANC) \>= 1.5 X 10\^9/L
• Hemoglobin (Hgb) \>= 9 g/dL (may transfuse if clinically indicated)
• Platelets (plt) \>= 100 x 10\^9/L
• Potassium within normal range, or correctable with supplements
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x upper limit normal (ULN) or =\< 5.0 x ULN if liver tumor is present
• Serum total bilirubin =\< 1.5 x ULN
• Serum creatinine =\< 1.5 x ULN, or 24-hr clearance \>= 60 ml/min
• Females of childbearing potential (defined as sexually mature women who):

You may not qualify if:

• Prior treatment with pembrolizumab or other PD-(L)1
• Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or current pneumonitis/ interstitial lung disease
• Has known active hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or hepatitis C (e.g., hepatitis C virus (HCV) ribonucleic acid (RNA) \[qualitative\] is detected)
• Has a history of hepatitis B virus (HBV)
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
• Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 6 weeks are allowed
• Persistent diarrhea or malabsorption \>= National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 2, despite medical management
• Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class 3 or 4 congestive heart failure
• Prior systemic cancer-directed treatments or investigational modalities =\< 5 half-lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from side effects of such therapy (except alopecia)
• Active autoimmune disease except for vitiligo or hypothyroidism
• Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis)
• Major surgery =\< 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy
• Pregnant or breastfeeding
• Known human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

pembrolizumab; Tamoxifen; Vorinostat

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Limitations and Caveats

The study closed early due to change in practice patterns

Results Point of Contact

• Title: Dr. Pamela Munster, MD
• Organization: University of California, San Francisco

pamela.munster@ucsf.edu

(415) 502-3598

Study Officials

• Pamela Munster, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2019
• First Posted: December 9, 2019
• Study Start: March 11, 2021
• Primary Completion: June 15, 2023
• Study Completion: June 15, 2023
• Last Updated: August 31, 2023
• Results First Posted: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)