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

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.

Conditions

• Clinical Stage II Esophageal Adenocarcinoma AJCC v8
• Clinical Stage III Esophageal Adenocarcinoma AJCC v8
• Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
• Clinical Stage IV Esophageal Adenocarcinoma AJCC v8
• Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
• Locally Advanced Esophageal Adenocarcinoma
• Locally Advanced Gastroesophageal Junction Adenocarcinoma
• Metastatic Esophageal Adenocarcinoma
• Metastatic Gastroesophageal Junction Adenocarcinoma
• Unresectable Esophageal Adenocarcinoma
• Unresectable Gastroesophageal Junction Adenocarcinoma

Interventions

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

Sponsors & Collaborators

• United States Department of Defense

  collaborator FED

• Roswell Park Cancer Institute

  lead OTHER

Principal Investigators

• Kannan Thanikachalam · Roswell Park Cancer Institute

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-03-07

Primary Completion

2029-03-30

Completion

2029-03-30

FDA Drug

Yes

Countries

• United States

Study Locations