Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma

Study Overview
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Brief Summary
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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 and will be considered separately as a single arm prospective cohort

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the safety and efficacy of propranolol hydrochloride (propranolol) in combination with standard neoadjuvant/definitive chemoradiation therapy (CRT) for esophageal cancer. SECONDARY OBJECTIVE: I. To estimate overall survival (OS) and pathologic response rate in patients that undergo surgery.

Official Title
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Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma A Phase II Study

Conditions
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Esophageal Adenocarcinoma

Intervention / Treatment
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* Drug: Carboplatin
* Radiation: 3 Dimensional Conformal Radiation Therapy
* Drug: Propranolol
* Radiation: Intensity Modulated Radiation Therapy
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemoradiation Therapy - Group I<br>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<br>* Given IV<br>* Other names: Ribocarbo;Radiation: 3 Dimensional Conformal Radiation Therapy<br>* Undergo 3D CRT<br>* Other names: Radiation;Radiation: Intensity Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: IMRT;Drug: Paclitaxel<br>* Given IV<br>* Other names: Taxol;|
| Active Comparator: Chemoradiation Therapy - Group II<br>Patients undergo CRT as in Group I in the absence of disease progression or unacceptable toxicity. | Radiation: 3 Dimensional Conformal Radiation Therapy<br>* Undergo 3D CRT<br>* Other names: Radiation;|
| Experimental: Chemoradiation Therapy plus Propanolol<br>Patients undergo radiation therapy as in Group I. Patients receive propranolol PO BID for 4-6 weeks while receiving CRT in the absence of disease progression or unacceptable toxicity. | Radiation: 3 Dimensional Conformal Radiation Therapy<br>* Undergo 3D CRT<br>* Other names: Radiation;Drug: Propranolol<br>* Subject will be treated with 30 mg po BID Propranolol for up to 6 weeks<br>* Other names: Innopran XL;Radiation: Intensity Modulated Radiation Therapy<br>* Undergo IMRT<br>* Other names: IMRT;|

What is the study measuring?
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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 |