Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma

Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma A Phase II Study

This phase II trial studies the side effects and best dose of propranolol when administered concurrently with SOC neoadjuvant CRT in patients with esophageal carcinoma, with a safety lead-in and dose expansion cohort. Patients who are already on β-blockers will receive standard of care CRT, or definitive chemotherapy or chemotherapy-immunotherapy and will be considered separately as a single arm prospective cohort

Study Overview

• Status: Recruiting
• Conditions: Esophageal Adenocarcinoma
• Intervention / Treatment: Drug: Carboplatin; Drug: Paclitaxel; Radiation: 3 Dimensional Conformal Radiation Therapy; Radiation: Intensity Modulated Radiation Therapy; Drug: Propranolol

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the safety and efficacy of propranolol hydrochloride (propranolol) in combination with standard neoadjuvant/definitive chemotherapy or chemotherapy-immunotherapy or chemoradiation therapy (CRT) for esophageal cancer.

SECONDARY OBJECTIVE:

I. To estimate overall survival (OS) and pathologic response rate in patients that undergo surgery.

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: ASK RPCI; Phone Number: 1-800-767-9355; Email: askroswell@roswellpark.org

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Undergoing definitive or neoadjuvant CRT for histologically confirmed esophageal adenocarcinoma
• Have an ECOG performance status of 0-1
• Have the ability to swallow and retain oral medication. If a patient is not able to swallow, they are still eligible for study provided they have an enteric feeding placed which will permit administration of crushed tablets or liquid formula propranolol prior to first radiation treatment
• 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.
• 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:

• Contraindications to the use of beta-blockers, e.g.; uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (New York Heart Association (NYHA) Grade III or IV), hypotension ( systolic blood pressure <100 mmHg), severe asthma or 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, current calcium channel blocker use (Non-dihydropyridines such as verapamil) or rhythm control agents such as digoxin and amiodarone. Patients with pacemakers will be excluded
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection,symptomatic congestive heart failure, unstable angina pectoris, psychiatric illness/social situations that would limit compliance with study requirements, cardiac arrhythmia (atrial fibrillation/flutter), severe bradycardia (heart rate of <50 beats per minute or 1st/ 2nd /3rd degree heart block)
• Pregnant or nursing female participants,
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemoradiation Therapy - Group I; Patients receiving beta-blockers undergo radiation therapy in the form of IMRT or 3D CRT over 23-28 fractions for 5 days per week (Monday-Friday) for 5 weeks, and receive paclitaxel IV QW and carboplatin IV QW for 5 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Carboplatin; Given IV; Other Names: Blastocarb; CBDCA; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Ribocarbo; (SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O'']platinum; Drug: Paclitaxel; Given IV; Other Names: Taxol; Anzatax; Bristaxol; Praxel; 33069-62-4; 5Beta,20-epoxy-1,2alpha; Radiation: 3 Dimensional Conformal Radiation Therapy; Undergo 3D CRT; Other Names: Radiation; 3D-CRT; Radiation: Intensity Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT
Active Comparator: Chemoradiation Therapy - Group II; Patients undergo CRT as in Group I in the absence of disease progression or unacceptable toxicity.	Radiation: 3 Dimensional Conformal Radiation Therapy; Undergo 3D CRT; Other Names: Radiation; 3D-CRT
Experimental: Chemoradiation Therapy plus Propanolol; Patients undergo radiation therapy as in Group I. Patients receive propranolol PO BID for 4-8 weeks while receiving standard neoadjuvant/definitive chemotherapy or chemotherapy-immunotherapy or CRT in the absence of disease progression or unacceptable toxicity.	Radiation: 3 Dimensional Conformal Radiation Therapy; Undergo 3D CRT; Other Names: Radiation; 3D-CRT; Radiation: Intensity Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT; Drug: Propranolol; Subject will be treated with 30 mg po BID Propranolol for up to 6 weeks; Other Names: Inderal; Innopran XL; 2-Propanol-1-[(1-methylethyl)amino]-3-(1-naphthalenyloxy) Hydrochloride; 318-98-9

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Adverse Events	To determine the safety and efficacy of the combination of propranolol plus chemoradiation	Up to 5 years
Progression Free Survival	Imaging findings from first radiation treatment to progression of disease	UP to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	will be assessed by chart review of date of last follow-up or date of death	Up to 5 years

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Anurag Singh, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2021
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: December 21, 2020
• First Submitted That Met QC Criteria: December 21, 2020
• First Posted (Actual): December 23, 2020

Study Record Updates

• Last Update Posted (Estimated): January 2, 2026
• Last Update Submitted That Met QC Criteria: December 30, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Adenocarcinoma Of Esophagus; Organic Chemicals; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Physical Phenomena; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amines; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Health Care Economics and Organizations; Alcohols; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Radiotherapy; Radiotherapy, Computer-Assisted; Economics; Carboplatin; Paclitaxel; Propranolol; Radiation; Radiotherapy, Intensity-Modulated; Radiotherapy, Conformal; Taxes; propranolol CR
• Other Study ID Numbers: I 630420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes