Trial Title:
Propranolol and Pembrolizumab for Tumor Re-sensitization and Treatment of Patients With Checkpoint Inhibitor Refractory Metastatic or Unresectable Triple Negative Breast Cancer
NCT ID:
NCT05741164
Condition:
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
Conditions: Official terms:
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Pembrolizumab
Propranolol
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo tumor biopsy
Arm group label:
Treatment (propranolol and pembrolizumab)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (propranolol and pembrolizumab)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (propranolol and pembrolizumab)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Treatment (propranolol and pembrolizumab)
Other name:
Keytruda
Other name:
Lambrolizumab
Other name:
MK-3475
Other name:
SCH 900475
Intervention type:
Drug
Intervention name:
Propranolol
Description:
Given PO
Arm group label:
Treatment (propranolol and pembrolizumab)
Other name:
1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Treatment (propranolol and pembrolizumab)
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 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:
I. 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:
I. 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:
I. 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.
Criteria for eligibility:
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 for patients with
creatinine levels greater than ULN
- 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Roswell Park Cancer Institute
Address:
City:
Buffalo
Zip:
14263
Country:
United States
Contact:
Last name:
Shipra Gandhi
Phone:
716-845-2544
Email:
Shipra.Gandhi@roswellpark.org
Investigator:
Last name:
Shipra Gandhi
Email:
Principal Investigator
Start date:
November 30, 2024
Completion date:
December 15, 2027
Lead sponsor:
Agency:
Roswell Park Cancer Institute
Agency class:
Other
Source:
Roswell Park Cancer Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05741164
