Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma

Roswell Park Comprehensive Cancer Center

Status and phase: Enrolling; Phase 2

Conditions: Esophageal Adenocarcinoma

Treatments: Drug: Carboplatin; Drug: Propranolol; Radiation: 3 Dimensional Conformal Radiation Therapy; Radiation: Intensity Modulated Radiation Therapy; Drug: Paclitaxel

Study type: Interventional

Funder types: Other

Identifiers

NCT04682158

I 630420

Details and patient eligibility

About

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

Full 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.

Enrollment: 106 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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106 participants in 3 patient groups

Chemoradiation Therapy - Group I

Active Comparator group

Description:

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.

Treatment:

Drug: Paclitaxel

Radiation: Intensity Modulated Radiation Therapy

Radiation: 3 Dimensional Conformal Radiation Therapy

Drug: Carboplatin

Chemoradiation Therapy - Group II

Active Comparator group

Description:

Patients undergo CRT as in Group I in the absence of disease progression or unacceptable toxicity.

Treatment:

Radiation: 3 Dimensional Conformal Radiation Therapy

Chemoradiation Therapy plus Propanolol

Experimental group

Description:

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.

Treatment:

Radiation: Intensity Modulated Radiation Therapy

Radiation: 3 Dimensional Conformal Radiation Therapy

Drug: Propranolol