Anatomic Stage III Breast Cancer AJCC v8Phase 2NCT05741164
Propranolol and Pembrolizumab for Tumor Re-sensitization and Treatment of Patients With Checkpoint Inhibitor Refractory Metastatic or Unresectable Triple Negative Breast Cancer
A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by Emory University at 2 sites in United States.
Trial summary
This phase II trial tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma
- What is being tested?
- Biopsy, Biospecimen Collection and Computed Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Sep 2024to 30 Jun 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years of age
- Have pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options
- No chemotherapy, radiotherapy, or major surgery within 4 weeks of protocol treatment
- Checkpoint inhibitor refractory patients (i.e., no longer responding to chemotherapy and checkpoint inhibitor) who have disease progression on prior line of chemotherapy and pembrolizumab, and, who in the opinion of the physician, can continue checkpoint inhibitor
- Patients must be agreeable to pre- and 6-week post treatment biopsy in part 1 of the study
- The pre-treatment biopsy for this study must be taken at least 4 weeks after all previous chemotherapy (pembrolizumab is allowed during this period)
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- Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 1
- Platelets >= 100,000/uL
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1500/uL
- Total bilirubin =< institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 X institutional ULN
- Creatinine clearance >= 50 mL/min per Cockcroft-Gault equation
- HbA1C <=8.5
- Have measurable disease per RECIST 1.1 criteria present
- Ability to swallow and retain oral medication
- Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
Who cannot join
- Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment
- Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
- Patients with rapidly progressive disease/ symptomatic disease
- Patients with primary resistance (i.e., did not respond to initial treatment with chemotherapy plus checkpoint inhibitor) with progressive disease at 12 weeks after starting chemotherapy and pembrolizumab
- Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening
- Participants with symptomatic known brain metastases < 4 weeks from radiation treatment should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
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- History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastases or death
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Unwilling or unable to follow protocol requirements
- Contraindications to the use of beta-blockers, like: uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (grade III or IV), hypotension (systolic blood pressure < 100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), uncontrolled type I or type II diabetes mellitus (hemoglobin A1C [HbA1C] > 8.5 or fasting plasma glucose > 160 mg/dl at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current use of beta-blockers or non-dihydropyridine calcium channel blockers
- Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 1 recruiting
- Recruiting
Emory University Hospital
Atlanta, Georgia, 30322
Kerry Dycus, 404-727-2527, kerry.dycus@emory.edu
Shipra Gandhi, MD, MS
- Withdrawn
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer
This phase II trial tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation. Beta-blockers, like propranolol, may help to counteract effects of certain stress hormones produced by the body during cancer treatment and may increase the effectiveness of the pembrolizumab. Pembrolizumab is a drug that is classified as an immune checkpoint inhibitor. 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. Propranolol may be able to re-sensitize the cells of the immune system to respond to the checkpoint inhibitor pembrolizumab in patients with checkpoint inhibitor refractory metastatic or unresectable triple negative breast cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- Determine the efficacy of propranolol on tumor re-sensitization, when given in combination with pembrolizumab in patients with checkpoint inhibitor refractory metastatic triple negative breast cancer.
SECONDARY OBJECTIVES:
- Assess 6-month progression-free and overall survival per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).
II. Safety and tolerability of propranolol when given in combination with pembrolizumab.
EXPLORATORY OBJECTIVES:
- Assess changes in immune markers (pre-treatment versus [vs] post-treatment) in biopsy and peripheral blood.
II. Correlate perceived stress scale with immune exhaustion markers and immune cells in the peripheral blood and tumor.
OUTLINE: Patients receive propranolol orally (PO) and pembrolizumab intravenously (IV) while on study. Patients undergo computed tomography (CT) scan, blood sample collection and may undergo tumor biopsy during screening and on study.
- Conditions
- Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Refractory Triple-Negative Breast Carcinoma, Unresectable Triple-Negative Breast Carcinoma
- Being tested
- Biopsy, Biospecimen Collection, Computed Tomography, Pembrolizumab, Propranolol
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyProcedure or surgery
Also called BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
Given IV
PropranololDrug
Also called 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (propranolol and pembrolizumab) | Experimental | Patients receive propranolol PO and pembrolizumab IV while on study. Patients undergo CT scan, blood sample collection and may undergo tumor biopsy during screening and on study. Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Pembrolizumab; Drug: Propranolol; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response
Efficacy as determined by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Will be summarized using frequencies and relative frequencies. The best response within the first 6 months will be determined as the best objective response.
Measured: Up to 6 months
Secondary outcomes (3)
Progression free survival
This will be summarized using standard Kaplan-Meier methods with 90% confidence intervals obtained for the median and 6-month rates.
Measured: The time treatment initiation until disease progression (per irRECIST), death due to any cause, subsequent therapies (treated as censored), or last follow-up, assessed up to 6 months
Overall survival
Measured per irRECIST. This will be summarized using standard Kaplan-Meier methods with 90% confidence intervals obtained for the median and 6-month rates.
Measured: The time from treatment initiation until death due to any cause or last follow-up, assessed up to 6 months
Incidence of adverse events of propranolol when given in combination with pembrolizumab
Toxicities and adverse events (as per Common Terminology Criteria for Adverse Events version 5.0) will be summarized by attribution and grade using frequencies and relative frequencies.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2023
- Study start1 Sep 2024
- Primary completion30 Jun 2028 (estimated)
- Study completion30 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage III Breast Cancer AJCC v8Studies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Shipra Gandhi, Emory University
- Investigators
- Shipra Gandhi, MD, MS, Principal investigator, Emory University Hospital/Winship Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05741164
- Sponsor's protocol ID
- STUDY00009637
- Other IDs
- NCI-2026-00570, I 2612022, K08CA279766, WINSHIP6621-25, 2025P012829
- Status last verified
- Jun 2026
- First submitted
- 14 Feb 2023
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT05741164
- Acronym / sponsor ID
- STUDY00009637
- Conditions
- Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Triple-Negative Breast Carcinoma, Refractory Triple-Negative Breast Carcinoma, Unresectable Triple-Negative Breast Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Sep 2024 (actual)
- Primary completion
- 30 Jun 2028 (estimated)
- Study completion
- 30 Jun 2029 (estimated)
- First posted
- 23 Feb 2023 (actual)
- Results
- Not posted in the source record
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 tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation. Beta-blockers, like propranolol, may help to counteract effects of certain stress hormones produced by the body during cancer treatment and may increase the effectiveness of the pembrolizumab. Pembrolizumab is a drug that is classified as an immune checkpoint inhibitor. 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. Propranolol may be able to re-sensitize the cells of the immune system to respond to the checkpoint inhibitor pembrolizumab in patients with checkpoint inhibitor refractory metastatic or unresectable triple negative breast cancer.
Detailed description
PRIMARY OBJECTIVE:
- Determine the efficacy of propranolol on tumor re-sensitization, when given in combination with pembrolizumab in patients with checkpoint inhibitor refractory metastatic triple negative breast cancer.
SECONDARY OBJECTIVES:
- Assess 6-month progression-free and overall survival per immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).
II. Safety and tolerability of propranolol when given in combination with pembrolizumab.
EXPLORATORY OBJECTIVES:
- Assess changes in immune markers (pre-treatment versus [vs] post-treatment) in biopsy and peripheral blood.
II. Correlate perceived stress scale with immune exhaustion markers and immune cells in the peripheral blood and tumor.
OUTLINE: Patients receive propranolol orally (PO) and pembrolizumab intravenously (IV) while on study. Patients undergo computed tomography (CT) scan, blood sample collection and may undergo tumor biopsy during screening and on study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (propranolol and pembrolizumab) | Experimental | Procedure: Biopsy, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Biological: Pembrolizumab, Drug: Propranolol, Other: Questionnaire AdministrationPatients receive propranolol PO and pembrolizumab IV while on study. Patients undergo CT scan, blood sample collection and may undergo tumor biopsy during screening and on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Age >= 18 years of age
- Have pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options
- No chemotherapy, radiotherapy, or major surgery within 4 weeks of protocol treatment
- Checkpoint inhibitor refractory patients (i.e., no longer responding to chemotherapy and checkpoint inhibitor) who have disease progression on prior line of chemotherapy and pembrolizumab, and, who in the opinion of the physician, can continue checkpoint inhibitor
- Patients must be agreeable to pre- and 6-week post treatment biopsy in part 1 of the study
Key exclusion criteria (11 listed)
- Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment
- Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
- Patients with rapidly progressive disease/ symptomatic disease
- Patients with primary resistance (i.e., did not respond to initial treatment with chemotherapy plus checkpoint inhibitor) with progressive disease at 12 weeks after starting chemotherapy and pembrolizumab
- Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening
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 |
|---|---|---|
| BiopsyAlso: BIOPSY_TYPE, BxUndergo tumor biopsy | Procedure or surgery | Treatment (propranolol and pembrolizumab) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (propranolol and pembrolizumab) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT scan | Procedure or surgery | Treatment (propranolol and pembrolizumab) |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Given IV | Biological | Treatment (propranolol and pembrolizumab) |
| PropranololAlso: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanolGiven PO | Drug | Treatment (propranolol and pembrolizumab) |
| Questionnaire AdministrationAncillary studies | Other | Treatment (propranolol and pembrolizumab) |
Primary outcome
Objective response
Time frame: Up to 6 months
Efficacy as determined by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Will be summarized using frequencies and relative frequencies. The best response within the first 6 months will be determined as the best objective response.
3 secondary outcomes
Progression free survival
Time frame: The time treatment initiation until disease progression (per irRECIST), death due to any cause, subsequent therapies (treated as censored), or last follow-up, assessed up to 6 months
Overall survival
Time frame: The time from treatment initiation until death due to any cause or last follow-up, assessed up to 6 months
Incidence of adverse events of propranolol when given in combination with pembrolizumab
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
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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.
Shipra Gandhi, MD, MS principal investigator
Emory University Hospital/Winship Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Anatomic Stage III Breast Cancer AJCC v8 and Anatomic Stage IV Breast Cancer AJCC v8, run by Emory University at 2 sites 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 18 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shipra Gandhi, MD, MS (404-778-1900, shipra.gandhi@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response (time frame: Up to 6 months). 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 4 Jun 2026.