Anatomic Stage IV Breast Cancer AJCC v8Phase 2NCT04190056
Pembrolizumab and Tamoxifen With or Without Vorinostat for the Treatment of Estrogen Receptor Positive Breast Cancer
A Phase 2 study testing Pembrolizumab, Tamoxifen and Vorinostat in people with Anatomic Stage IV Breast Cancer AJCC v8 and Prognostic Stage IV Breast Cancer AJCC v8, run by University of California, San Francisco at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anatomic Stage IV Breast Cancer AJCC v8, Prognostic Stage IV Breast Cancer AJCC v8
- What is being tested?
- Pembrolizumab, Tamoxifen and Vorinostat
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Mar 2021to 15 Jun 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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):
- Has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or,
- Has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months) must have
- Negative serum pregnancy test within 14 days before starting study treatment in females of childbearing potential (FCBP) and willingness to adhere to acceptable forms or birth control (a physician-approved contraceptive method (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner)
- All female and male participants must agree to use approved contraception during the treatment period and for at least 18 weeks after the last dose of study treatment and refrain from donating sperm during this period
Who cannot join
- 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
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- 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
- Known history of tuberculosis
- Known allergic reaction or intolerability to tamoxifen
- Patients with prior history of deep vein thrombosis (DVT)s must be on therapeutic or preventive anticoagulation
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California, 94143
About this study
Official title: Epigenetic Priming for Immune Therapy in ER-Positive Breast Cancer in Biomarker Select Population
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To define the role of epigenetic immune priming in a biomarker enriched estrogen receptor (ER)+ breast cancer population on the basis of overall response rate.
SECONDARY OBJECTIVES:
- To assess duration of response (DOR) 24-week landmark progression-free survival (PFS:24).
II. Median PFS and overall survival (OS). III. Tumor responses will also be calculated by Immune Related Response-Criteria (irRC).
EXPLORATORY OBJECTIVES:
- Evaluation of biomarker target threshold on response rate (retrospective cut off of 20% versus [vs] 10%).
II. To assess the ratio of effector T cells: regulatory T cells in blood and tumor biopsies pre- and post-therapy.
III. To evaluate inflammatory T cell signature changes in blood and tumor biopsies pre- and post-therapy.
IV. To evaluate changes in number of myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor biopsies pre- and posttherapy.
- To evaluate changes in histone acetylation in peripheral blood cells and tumor biopsies pre- and post-therapy.
VI. Initial comparison to vorinostat-induced PD-1 in lymphocytes, PD-L1 modulation.
VII. Nanostring and 10 x sequencing and single cell immune phenotyping (on stored tissue for successful arms only).
VIII. Impact of histone deacetylase (HDAC) inhibition of response to pembrolizumab vs. pembrolizumab in biomarker enriched population.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, vorinostat orally (PO) once daily (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.
ARM B: 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.
After completion of study treatment, patients are followed up for 30 days and then every 12 weeks thereafter.
- Being tested
- Pembrolizumab, Tamoxifen, Vorinostat
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
TamoxifenDrug
Given PO
VorinostatDrug
Also called L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Pembrolizumab; Drug: Tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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,.
Measured: Up to 24 weeks
Secondary outcomes (4)
Percentage of Participants With Tumor Responses
Tumor responses will be classified using the Immune Related Response-Criteria (irRC)) through study completion.
Measured: Up to 24 months
Duration of Response (DOR)
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented. Duration of stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since the treatment started. Will use median DOR (computed by the Kaplan-Meier estimator) to summarize. The respective confidence intervals will be computed as well.
Measured: Up to 24 weeks
Median Progression Free Survival (PFS)
Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression or death from any cause on study, whichever occurs first. Will use median PFS (computed by the Kaplan-Meier estimator) to summarize. The respective confidence intervals will be computed as well.
Measured: Up to 27 months
Median Overall Survival (OS)
Will use median OS (computed by the Kaplan-Meier estimator) to summarize from initiation of study treatment to the time of death from any cause on study. The respective confidence intervals will be computed as well.
Measured: Up to 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2019
- Study start11 Mar 2021
- Primary completion15 Jun 2023
- Study completion15 Jun 2023
Why it stopped: Change in practice patterns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Anatomic Stage IV Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Pamela Munster, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04190056
- Sponsor's protocol ID
- 197520
- Other IDs
- NCI-2019-07572
- Status last verified
- Aug 2023
- First submitted
- 4 Dec 2019
- Last updated
- 31 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Priming for Immune Therapy in ER-Positive Breast Cancer in Biomarker Select Population
- ClinicalTrials.gov ID
- NCT04190056
- Acronym / sponsor ID
- 197520
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Change in practice patterns
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 11 Mar 2021 (actual)
- Primary completion
- 15 Jun 2023 (actual)
- Study completion
- 15 Jun 2023 (actual)
- First posted
- 9 Dec 2019 (actual)
- Results
- Posted 31 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To define the role of epigenetic immune priming in a biomarker enriched estrogen receptor (ER)+ breast cancer population on the basis of overall response rate.
SECONDARY OBJECTIVES:
- To assess duration of response (DOR) 24-week landmark progression-free survival (PFS:24).
II. Median PFS and overall survival (OS). III. Tumor responses will also be calculated by Immune Related Response-Criteria (irRC).
EXPLORATORY OBJECTIVES:
- Evaluation of biomarker target threshold on response rate (retrospective cut off of 20% versus [vs] 10%).
II. To assess the ratio of effector T cells: regulatory T cells in blood and tumor biopsies pre- and post-therapy.
III. To evaluate inflammatory T cell signature changes in blood and tumor biopsies pre- and post-therapy.
IV. To evaluate changes in number of myeloid-derived suppressor cells (MDSCs) in peripheral blood and tumor biopsies pre- and posttherapy.
- To evaluate changes in histone acetylation in peripheral blood cells and tumor biopsies pre- and post-therapy.
VI. Initial comparison to vorinostat-induced PD-1 in lymphocytes, PD-L1 modulation.
VII. Nanostring and 10 x sequencing and single cell immune phenotyping (on stored tissue for successful arms only).
VIII. Impact of histone deacetylase (HDAC) inhibition of response to pembrolizumab vs. pembrolizumab in biomarker enriched population.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1, vorinostat orally (PO) once daily (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.
ARM B: 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.
After completion of study treatment, patients are followed up for 30 days and then every 12 weeks thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (pembrolizumab, vorinostat, tamoxifen) | Experimental | Biological: Pembrolizumab, Drug: Tamoxifen, Drug: VorinostatPatients 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. |
| Arm B (pembrolizumab, tamoxifen) | Experimental | Biological: Pembrolizumab, Drug: TamoxifenPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Arm A (pembrolizumab, vorinostat, tamoxifen), Arm B (pembrolizumab, tamoxifen) |
| TamoxifenGiven PO | Drug | Arm A (pembrolizumab, vorinostat, tamoxifen), Arm B (pembrolizumab, tamoxifen) |
| VorinostatAlso: L-001079038, MSK-390, SAHA, Suberanilohydroxamic AcidGiven PO | Drug | Arm A (pembrolizumab, vorinostat, tamoxifen) |
Primary outcome
Overall Response Rate (ORR)
Time frame: Up to 24 weeks
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,.
4 secondary outcomes
Percentage of Participants With Tumor Responses
Time frame: Up to 24 months
Duration of Response (DOR)
Time frame: Up to 24 weeks
Median Progression Free Survival (PFS)
Time frame: Up to 27 months
Median Overall Survival (OS)
Time frame: Up to 27 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pamela Munster, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab, Tamoxifen and Vorinostat in people with Anatomic Stage IV Breast Cancer AJCC v8 and Prognostic Stage IV Breast Cancer AJCC v8, run by University of California, San Francisco at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.