- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05651594
Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma
A Phase 2 Trial of Chemotherapy, Pembrolizumab, and Propranolol in Advanced Esophageal/Gastroesophageal Junction Adenocarcinoma Patients
Study Overview
Status
Conditions
- Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8
- Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8
- Metastatic Gastroesophageal Junction Adenocarcinoma
- Unresectable Gastroesophageal Junction Adenocarcinoma
- Locally Advanced Gastroesophageal Junction Adenocarcinoma
- Clinical Stage II Esophageal Adenocarcinoma AJCC v8
- Clinical Stage III Esophageal Adenocarcinoma AJCC v8
- Clinical Stage IV Esophageal Adenocarcinoma AJCC v8
- Metastatic Esophageal Adenocarcinoma
- Unresectable Esophageal Adenocarcinoma
- Locally Advanced Esophageal Adenocarcinoma
Detailed Description
PRIMARY OBJECTIVE:
I. To determine the clinical efficacy of propranolol in combination with pembrolizumab and standard chemotherapy in frontline metastatic esophageal or gastroesophageal junction (GEJ) adenocarcinoma.
SECONDARY OBJECTIVE:
I. To evaluate the progression-free survival, overall survival, overall response rate, and safety profile of the combination of pembrolizumab and propranolol with standard chemotherapy.
EXPLORATORY OBJECTIVE:
I. To correlate baseline or changes in the levels of biomarkers (e.g., like, peripheral T-cell subsets/myeloid-derived suppressor cells [MDSC]/cytokines), perceived stress and exercise Perceived Stress Scale (PSS) with efficacy (overall response rate [ORR], progression-free survival [PFS], overall survival [OS]), and chronotropic effect of exercise.
OUTLINE:
Patients receive mFOLFOX6 (leucovorin intravenously [IV], oxaliplatin IV, and fluorouracil IV), pembrolizumab IV, and propranolol orally (PO) on study. Patients also undergo tumor biopsy during screening and computed tomography (CT) scans and collection of blood samples during screening and on study.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
Buffalo, New York, United States, 14263
- Recruiting
- Roswell Park Cancer Institute
-
Principal Investigator:
- Sarbajit Mukherjee
-
Contact:
- Sarbajit Mukherjee
- Phone Number: 716-845-7405
- Email: Sarbajit.Mukherjee@RoswellPark.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age >= 18 years of age.
- Participants must be newly diagnosed, treatment-naive with unresectable locally advanced or metastatic esophageal/gastroesophageal junction (GEJ) adenocarcinoma. Any prior systemic treatment for resectable disease must be six months or before. Prior PD-1/PD-L1 treatment is allowed as long as the treatment was completed more than 1 year ago.
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
- Available archival Formalin-Fixed Paraffin-Embedded (FFPE) from a prior biopsy collected within 1 year or, participant must be willing to have a tissue biopsy taken prior to start of study treatment.
- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present.
- Platelet >= 75,000/uL
- Hemoglobin >= 8 g/dL (without transfusion in the past 14 days)
- Absolute Neutrophil Count (ANC) >= 1500/uL
- Creatinine clearance (Cockcroft Gault) >= 30 mL/min
- Total bilirubin: =< 2 × upper limit of normal (ULN) OR direct bilirubin =< ULN for participants with total bilirubin levels > 2 × ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase) (SGOT) and alanine transaminase (ALT) (serum glutamic-pyruvic transaminase) (SGPT) =< 3 X institutional ULN (=< 5 × ULN for participants with liver metastases)
- 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.
- 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.
- 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:
- Patients with HER 2-positive cancer.
- Patients with active, untreated central nervous system metastases or leptomeningeal disease.
Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation.
- Patients currently treated with systemic immunosuppressive agents: If a patient is currently on steroids, they must be on a steroid dose less than or equal to an equivalent prednisone dose of 10 mg daily.
- Has a history of (non-infectious) pneumonitis/interstitial lung disease that required treatment.
- Has a concurrent Human Immunodeficiency Virus (HIV) infection.
- Concurrent active Hepatitis B (defined as Hepatitis B virus surface antigen [HBsAg] positive and/or detectable Hepatitis B virus [HBV] deoxyribonucleic acid DNA) and Hepatitis C virus (defined as anti-HCV antibody [Ab] positive and detectable HCV ribonucleic acid [RNA]) infection. Note: Hepatitis B and C screening tests are not required unless known history of HBV and HCV infection.
- Participants that are already on beta-adrenergic (B-AR) blockers for various indications.
- Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=<2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or nursing female participants, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test.
- Other active cancers that require systemic treatment.
- Contraindications to the use of beta-blockers, e.g.: uncontrolled depression, unstable angina pectoris, uncontrolled heart failure ( Grade III or IV), hypotension (systolic blood pressure <100 mmHg), severe asthma or chronic obstructive pulmonary disease (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 etc.
- Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of trial treatment and while participating in the trial. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster etc.
- 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: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (mFOLFOX6, pembrolizumab, propranolol)
Patients receive mFOLFOX6 (leucovorin IV, oxaliplatin IV, and fluorouracil IV), pembrolizumab IV, and propranolol PO on study.
Patients also undergo tumor biopsy during screening and CT scans and collection of blood samples during screening and on study.
|
Undergo collection of blood samples
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Undergo CT scans
Other Names:
Undergo tissue collection
Other Names:
Perceived Stress Scale
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall response rate (ORR)
Time Frame: Within 6 months of initiating combination therapy
|
Efficacy of pembrolizumab in combination with propranolol with standard chemotherapy measured by ORR by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, which is treated as a dichotomous variable and will be summarized using frequencies and relative frequencies.
|
Within 6 months of initiating combination therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of toxicities and adverse events
Time Frame: Up to 30 days after the last intervention
|
Will be assessed as per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
|
Up to 30 days after the last intervention
|
Progression-free survival
Time Frame: Initiation of the study treatment regimen to disease progression or death from any cause, assessed up to 2 years
|
Will be summarized using standard Kaplan Meier methods.
|
Initiation of the study treatment regimen to disease progression or death from any cause, assessed up to 2 years
|
Overall survival
Time Frame: Treatment initiation until death from any cause, assessed up to 2 years
|
Will be summarized using standard Kaplan Meier methods.
|
Treatment initiation until death from any cause, assessed up to 2 years
|
ORR
Time Frame: Within 6 months of initiating combination therapy
|
ORR as determined by Immune-Modified (i)RECIST.
|
Within 6 months of initiating combination therapy
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Sarbajit Mukherjee, Roswell Park Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Head and Neck Neoplasms
- Esophageal Diseases
- Adenocarcinoma
- Esophageal Neoplasms
- Physiological Effects of Drugs
- Adrenergic beta-Antagonists
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Antihypertensive Agents
- Vasodilator Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Antineoplastic Agents, Immunological
- Micronutrients
- Vitamins
- Immune Checkpoint Inhibitors
- Antidotes
- Vitamin B Complex
- Propranolol
- Fluorouracil
- Oxaliplatin
- Pembrolizumab
- Leucovorin
Other Study ID Numbers
- I 2734222 (Other Identifier: Roswell Park Cancer Institute)
- NCI-2022-09209 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- W81XWH2210916 (Other Grant/Funding Number: DOD)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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