Using propranolol and pembrolizumab to treat resistant triple negative breast cancer
Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer
This study is testing if adding propranolol to pembrolizumab can help people with hard-to-treat triple negative breast cancer respond better to their treatment.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 37 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | Roswell Park Cancer Institute Academic / other |
| Drugs / interventions | pembrolizumab, chemotherapy, radiation, Immunotherapy |
| Locations | 1 site (Buffalo, New York) |
| Trial ID | NCT05741164 on ClinicalTrials.gov |
What this trial studies
This phase II trial investigates the effectiveness of propranolol, a beta-blocker, in combination with pembrolizumab, an immune checkpoint inhibitor, for patients with metastatic or unresectable triple negative breast cancer that has not responded to previous treatments. The study aims to determine if propranolol can help re-sensitize tumors to pembrolizumab, potentially improving treatment outcomes. Participants will undergo biopsies and imaging to assess tumor response and immune markers before and after treatment.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with unresectable or metastatic triple negative breast cancer that has shown no response to prior checkpoint inhibitor therapy.
Not a fit: Patients who have not been diagnosed with triple negative breast cancer or those who have not received prior checkpoint inhibitor therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new treatment option for patients with difficult-to-treat triple negative breast cancer.
How similar studies have performed: While the combination of propranolol and pembrolizumab is a novel approach, previous studies have shown promise in using immune checkpoint inhibitors for similar cancer types.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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) * 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 Exclusion Criteria: * 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 * 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
Where this trial is running
Buffalo, New York
- Roswell Park Cancer Institute — Buffalo, New York, United States (Recruiting)
Study contacts
- Principal investigator: Sheheryar Kabraji — Roswell Park Cancer Institute
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.