A Phase 2 Trial of Chemotherapy, Pembrolizumab, and Propranolol in Advanced Esophageal/Gastroesophageal Junction Adenocarcinoma Patients
Roswell Park Cancer Institute
Summary
This phase II trial tests what effects the addition of propranolol to pembrolizumab and standard chemotherapy (mFOLFOX) may have on response to treatment in patients with esophageal or gastroesophageal junction cancer that cannot be removed by surgery and has spread to nearby tissue or lymph nodes (unresectable locally advanced) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation (blood flow through arteries and veins). Cancer patients may be under a tremendous amount of stress with elevated levels of norepinephrine (a hormone produced by the adrenal glands in response to stress). Increased adrenergic stress may dampen the immune system, which beta-blockers, like propranolol, may be able to counteract. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in the standard chemotherapy regimen, mFOLFOX (leucovorin, fluorouracil and oxaliplatin) work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Adding propranolol to pembrolizumab and standard mFOLFOX chemotherapy may increase the effectiveness of the pembrolizumab + mFOLFOX regimen.
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 \[MDSC\]/cy…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- ProcedureBiopsy
Undergo tissue collection
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureComputed Tomography
Undergo CT scans
- DrugFluorouracil
Given IV
- DrugLeucovorin
Given IV
- DrugOxaliplatin
Given IV
- BiologicalPembrolizumab
Given IV
Location
- Roswell Park Cancer InstituteBuffalo, New York