Actively Recruiting

Phase 2
Age: 18Years +
All Genders
NCT05651594

Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma

Led by Roswell Park Cancer Institute · Updated on 2025-12-16

40

Participants Needed

1

Research Sites

316 weeks

Total Duration

On this page

Sponsors

R

Roswell Park Cancer Institute

Lead Sponsor

U

United States Department of Defense

Collaborating Sponsor

AI-Summary

What this Trial Is About

This phase II trial tests what effects the addition of propranolol to pembrolizumab and standard chemotherapy (mFOLFOX) may have on response to treatment in patients with esophageal or gastroesophageal junction cancer that cannot be removed by surgery and has spread to nearby tissue or lymph nodes (unresectable locally advanced) 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 (blood flow through arteries and veins). Cancer patients may be under a tremendous amount of stress with elevated levels of norepinephrine (a hormone produced by the adrenal glands in response to stress). Increased adrenergic stress may dampen the immune system, which beta-blockers, like propranolol, may be able to counteract. 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. Drugs used in the standard chemotherapy regimen, mFOLFOX (leucovorin, fluorouracil and oxaliplatin) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding propranolol to pembrolizumab and standard mFOLFOX chemotherapy may increase the effectiveness of the pembrolizumab + mFOLFOX regimen.

CONDITIONS

Official Title

Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 18 years or older
  • Newly diagnosed, treatment-naive with unresectable locally advanced or metastatic esophageal/gastroesophageal junction adenocarcinoma
  • Prior systemic treatment for resectable disease allowed if given 6 months or more ago
  • Prior PD-1/PD-L1 treatment allowed if completed more than 1 year ago
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Available archival biopsy tissue within 1 year or willingness to have biopsy before treatment
  • Measurable disease by RECIST 1.1 criteria
  • Platelet count of 75,000/uL or higher
  • Hemoglobin 8 g/dL or higher without transfusion in past 14 days
  • Absolute neutrophil count (ANC) 1500/uL or higher
  • Creatinine clearance of 30 mL/min or higher
  • Total bilirubin less than or equal to 2 times upper limit of normal (ULN) or direct bilirubin less than or equal to ULN if total bilirubin is higher
  • AST and ALT less than or equal to 3 times institutional ULN (or 5 times ULN if liver metastases present)
  • Negative pregnancy test for women of childbearing potential and agreement to use contraception
  • Ability to swallow and retain oral medication or use liquid/feeding tube propranolol
  • Understanding of study and signed informed consent
Not Eligible

You will not qualify if you...

  • HER 2-positive cancer
  • Active, untreated central nervous system metastases or leptomeningeal disease
  • Active autoimmune disease requiring immunosuppressive therapy or history of transplantation
  • Current systemic immunosuppressive treatment exceeding prednisone 10 mg daily equivalent
  • History of pneumonitis or interstitial lung disease requiring treatment
  • HIV infection
  • Active Hepatitis B or C infection
  • Current use of beta-blockers
  • Radiotherapy within 2 weeks before study treatment without recovery
  • Uncontrolled illnesses like infections, heart failure, unstable angina, arrhythmia, or psychiatric/social issues limiting compliance
  • Pregnant or nursing female participants
  • Other active cancers needing systemic treatment
  • Contraindications to beta-blockers including uncontrolled depression, heart failure grade III/IV, low blood pressure, severe asthma/COPD, uncontrolled diabetes, peripheral arterial disease, untreated pheochromocytoma
  • Receipt of live vaccine within 30 days before first dose
  • Inability or unwillingness to follow study requirements
  • Any condition making participant unsuitable for study drug per investigator's opinion

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Trial Site Locations

Total: 1 location

1

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

Actively Recruiting

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How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma | DecenTrialz