Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma
NCT ID: NCT05651594
Last Updated: 2025-12-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE2
40 participants
INTERVENTIONAL
2023-03-07
2029-03-30
Brief Summary
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Detailed Description
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I. To determine the clinical efficacy of propranolol in combination with pembrolizumab and standard chemotherapy in frontline metastatic esophageal or gastroesophageal junction (GEJ) adenocarcinoma.
SECONDARY OBJECTIVE:
I. To evaluate the progression-free survival, overall survival, overall response rate, and safety profile of the combination of pembrolizumab and propranolol with standard chemotherapy.
EXPLORATORY OBJECTIVE:
I. To correlate baseline or changes in the levels of biomarkers (e.g., like, peripheral T-cell subsets/myeloid-derived suppressor cells \[MDSC\]/cytokines), perceived stress and exercise Perceived Stress Scale (PSS) with efficacy (overall response rate \[ORR\], progression-free survival \[PFS\], overall survival \[OS\]), and chronotropic effect of exercise.
OUTLINE:
Patients receive mFOLFOX6 (leucovorin intravenously \[IV\], oxaliplatin IV, and fluorouracil IV), pembrolizumab IV, and propranolol orally (PO) on study. Patients also undergo tumor biopsy during screening and computed tomography (CT) scans and collection of blood samples during screening and on study.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (mFOLFOX6, pembrolizumab, propranolol)
Patients receive mFOLFOX6 (leucovorin IV, oxaliplatin IV, and fluorouracil IV), pembrolizumab IV, and propranolol PO on study. Patients also undergo tumor biopsy during screening and CT scans and collection of blood samples during screening and on study.
Biopsy
Undergo tissue collection
Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT scans
Fluorouracil
Given IV
Leucovorin
Given IV
Oxaliplatin
Given IV
Pembrolizumab
Given IV
Propranolol Hydrochloride
Given PO
Questionnaire Administration
Perceived Stress Scale
Interventions
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Biopsy
Undergo tissue collection
Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT scans
Fluorouracil
Given IV
Leucovorin
Given IV
Oxaliplatin
Given IV
Pembrolizumab
Given IV
Propranolol Hydrochloride
Given PO
Questionnaire Administration
Perceived Stress Scale
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Participants must be newly diagnosed, treatment-naive with unresectable locally advanced or metastatic esophageal/gastroesophageal junction (GEJ) adenocarcinoma. Any prior systemic treatment for resectable disease must be six months or before. Prior PD-1/PD-L1 treatment is allowed as long as the treatment was completed more than 1 year ago.
* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
* Available archival Formalin-Fixed Paraffin-Embedded (FFPE) from a prior biopsy collected within 1 year or, participant must be willing to have a tissue biopsy taken prior to start of study treatment.
* Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present.
* Platelet \>= 75,000/uL
* Hemoglobin \>= 8 g/dL (without transfusion in the past 14 days)
* Absolute Neutrophil Count (ANC) \>= 1500/uL
* Creatinine clearance (Cockcroft Gault) \>= 30 mL/min
* Total bilirubin: =\< 2 × upper limit of normal (ULN) OR direct bilirubin =\< ULN for participants with total bilirubin levels \> 2 × ULN
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase) (SGOT) and alanine transaminase (ALT) (serum glutamic-pyruvic transaminase) (SGPT) =\< 3 X institutional ULN (=\< 5 × ULN for participants with liver metastases)
* Participants of child-bearing potential must have a negative pregnancy test at study entry and then 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.
* Ability to swallow and retain oral medication. If a patient is not able to swallow or is experiencing dysphagia that limits ability to swallow oral medication, they are still eligible for study provided they can swallow liquid formula propranolol or have an enteric feeding tube placed which will permit administration of crushed tablets or liquid formula propranolol. Liquid and tablet formulations may be used interchangeably for patients in the event of a shortage of either formulation
* 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 with active, untreated central nervous system metastases or leptomeningeal disease.
* Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation.
* Patients currently treated with systemic immunosuppressive agents: If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily.
* Has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment.
* Has a concurrent Human Immunodeficiency Virus (HIV) infection.
* Concurrent active Hepatitis B (defined as Hepatitis B virus surface antigen \[HBsAg\] positive and/or detectable Hepatitis B virus \[HBV\] deoxyribonucleic acid DNA) and Hepatitis C virus (defined as anti-HCV antibody \[Ab\] positive and detectable HCV ribonucleic acid \[RNA\]) infection. Note: Hepatitis B and C screening tests are not required unless known history of HBV and HCV infection.
* Participants that are already on beta-adrenergic (B-AR) blockers for various indications.
* Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\<2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
* 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.
* Pregnant or nursing female participants, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
* Other active cancers that require systemic treatment.
* Contraindications to the use of beta-blockers, e.g.: 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 (HbA1C \> 8.5 or fasting plasma glucose \> 160 mg/dl at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma etc.
* Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster etc.
* Unwilling or unable to follow protocol requirements.
* Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug.
18 Years
ALL
No
Sponsors
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United States Department of Defense
FED
Roswell Park Cancer Institute
OTHER
Responsible Party
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Principal Investigators
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Kannan Thanikachalam
Role: PRINCIPAL_INVESTIGATOR
Roswell Park Cancer Institute
Locations
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Roswell Park Cancer Institute
Buffalo, New York, United States
Countries
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Facility Contacts
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Other Identifiers
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NCI-2022-09209
Identifier Type: REGISTRY
Identifier Source: secondary_id
I 2734222
Identifier Type: OTHER
Identifier Source: secondary_id
W81XWH2210916
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
I 2734222
Identifier Type: -
Identifier Source: org_study_id