Ignite Creation Date:
2025-12-25 @ 1:33 AM
Ignite Modification Date:
2025-12-26 @ 2:07 AM
Study NCT ID:
NCT05651594
Status:
RECRUITING
Last Update Posted:
2025-12-16
First Post:
2022-12-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma
Sponsor:
Roswell Park Cancer Institute
Organization:
Study Overview
Official Title:
A Phase 2 Trial of Chemotherapy, Pembrolizumab, and Propranolol in Advanced Esophageal/Gastroesophageal Junction Adenocarcinoma Patients
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?: