RECRUITING

Propranolol and Pembrolizumab for Tumor Re-sensitization and Treatment of Patients With Checkpoint Inhibitor Refractory Metastatic or Unresectable Triple Negative Breast Cancer

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Conditions

Anatomic Stage III Breast Cancer AJCC v8Anatomic Stage IV Breast Cancer AJCC v8Metastatic Triple-Negative Breast CarcinomaRefractory Triple-Negative Breast CarcinomaUnresectable Triple-Negative Breast Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Impact of Beta-2 Adrenergic Blockade With Checkpoint Inhibition in Checkpoint Inhibitor Refractory Metastatic Triple Negative Breast Cancer

Quick Facts

Study Start:2024-10-22
Study Completion:2027-12-15
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05741164

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:FEMALE
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Age \>= 18 years of age
  2. * Have pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options
  3. * No chemotherapy, radiotherapy, or major surgery within 4 weeks of protocol treatment
  4. * 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
  5. * Patients must be agreeable to pre- and 6-week post treatment biopsy in part 1 of the study
  6. * The pre-treatment biopsy for this study must be taken at least 4 weeks after all previous chemotherapy (pembrolizumab is allowed during this period)
  7. * 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
  8. * Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 1
  9. * Platelets \>= 100,000/uL
  10. * Hemoglobin \>= 9.0 g/dL
  11. * Absolute neutrophil count (ANC) \>= 1500/uL
  12. * Total bilirubin =\< institutional upper limit of normal (ULN)
  13. * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional ULN
  14. * Creatinine clearance \>= 50 mL/min per Cockcroft-Gault equation for patients with creatinine levels greater than ULN
  15. * Have measurable disease per RECIST 1.1 criteria present
  16. * Ability to swallow and retain oral medication
  17. * 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
  1. * Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment
  2. * Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
  3. * Patients with rapidly progressive disease/ symptomatic disease
  4. * 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
  5. * Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening
  6. * 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
  7. * 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
  8. * 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
  9. * Unwilling or unable to follow protocol requirements
  10. * 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
  11. * Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs

Contacts and Locations

Principal Investigator

Shipra Gandhi
PRINCIPAL_INVESTIGATOR
Roswell Park Cancer Institute

Study Locations (Sites)

Roswell Park Cancer Institute
Buffalo, New York, 14263
United States

Collaborators and Investigators

Sponsor: Roswell Park Cancer Institute

  • Shipra Gandhi, PRINCIPAL_INVESTIGATOR, Roswell Park Cancer Institute

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-10-22
Study Completion Date2027-12-15

Study Record Updates

Study Start Date2024-10-22
Study Completion Date2027-12-15

Terms related to this study

Additional Relevant MeSH Terms

  • 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