Esophageal Adenocarcinoma
Conditions
Brief summary
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
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.
Interventions
DRUGCarboplatin
Given IV
RADIATION3 Dimensional Conformal Radiation Therapy
Undergo 3D CRT
DRUGPropranolol
Subject will be treated with 30 mg po BID Propranolol for up to 6 weeks
RADIATIONIntensity Modulated Radiation Therapy
Undergo IMRT
DRUGPaclitaxel
Given IV
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Adverse Events | Up to 5 years | To determine the safety and efficacy of the combination of propranolol plus chemoradiation |
| Progression Free Survival | UP to 5 years | Imaging findings from first radiation treatment to progression of disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 5 years | will be assessed by chart review of date of last follow-up or date of death |
Countries
United States
Contacts
Primary ContactASK RPCI
Outcome results
None listed