Trials / Recruiting

RecruitingNCT05651594

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

A Phase 2 Trial of Chemotherapy, Pembrolizumab, and Propranolol in Advanced Esophageal/Gastroesophageal Junction Adenocarcinoma Patients

Status: Recruiting
Phase: Phase 2
Study type: Interventional
Enrollment: 40 (estimated)

Sponsor: Roswell Park Cancer Institute · Academic / Other
Sex: All
Age: 18 Years
Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVE: 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

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo tissue collection
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT scans
DRUG	Fluorouracil	Given IV
DRUG	Leucovorin	Given IV
DRUG	Oxaliplatin	Given IV
BIOLOGICAL	Pembrolizumab	Given IV
DRUG	Propranolol Hydrochloride	Given PO
OTHER	Questionnaire Administration	Perceived Stress Scale

Timeline

Start date: 2023-03-07
Primary completion: 2029-03-30
Completion: 2029-03-30
First posted: 2022-12-15
Last updated: 2025-12-16

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05651594. Inclusion in this directory is not an endorsement.