To evaluate the antitumor activity and safety/tolerability of the combination (mFOLFOX + Pembrolizumab) in patients with potentially resectable adenocarcinoma of the Gastroesophageal Junction (GEJ) and stomach.
This study will evaluate the efficacy and safety of perioperative mFOLFOX plus Pembrolizumab combination regimen in participants with potentially resectable adenocarcinoma of the GEJ and stomach. * The study is a non-randomized, open-label, single-arm phase II study. * The enrolled participants will receive neoadjuvant combination of mFOLFOX every 2 weeks for 4 doses (on Days 1, 15, 29, 43) and Pembrolizumab every 3 weeks for 3 doses (on Days 1, 22, 43). * Serious adverse events (SAEs) will be assessed on an ongoing basis using CTCAE v4.0, and the Thall, Simon, and Estey's design to monitor the efficacy and toxicity continuously together. * Repeat PET-CT will be obtained approximately 2-3 weeks after completion of neoadjuvant combination therapy. * If no evidence of metastatic disease on PET-CT, participants will undergo potentially curative surgical resection 4-6 weeks after completion of neoadjuvant combination therapy. This will be followed by adjuvant combination therapy (to be started 6-8 weeks after surgery) consisting of mFOLFOX every 2 weeks for additional 4 doses (total 4 months of therapy) plus Pembrolizumab every 3 weeks for additional 12 doses (total 1 year of therapy). If there is evidence of metastatic disease on PET-CT, participant will come off the study (i.e., will not undergo surgical resection and adjuvant therapy). * Participants will continue to receive treatment until either one of the following occurs: completion of adjuvant therapy, development of radiographically confirmed progression, participant withdraws consent, intercurrent illness that prevents further administration of treatment, or sponsor-investigator decides to withdraw the participant. * Efficacy outcomes during the adjuvant chemotherapy phase will be determined by radiologic measurements by CT using RECIST v1.1. Assessment of response will be performed every 3 months for the first year and as per the standard institutional guidelines thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Pembrolizumab, mFOLFOX Chemotherapy
Pembrolizumab, mFOLFOX Chemotherapy
The University of Kansas Cancer Center
Westwood, Kansas, United States
Pathological response rate (ypRR)
Number of participants with ypRR after neoadjuvant therapy. Will be assessed on the surgical resection specimen after neoadjuvant therapy, using Haemotoxylin and Eosin (H\&E) staining and evaluated using Tumor Regression Score.
Time frame: 10-14 weeks
Number of Adverse Events related to toxicity.
Number of participants with adverse events related to toxicity. Evaluated using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Participants will be followed for adverse event monitoring through the final safety follow up visit or until study discontinuation/disease progression, whichever occurs first.
Time frame: up to 14 months
Objective response rate (ORR)
Number of participants with ORR (partial response and complete response) at 12 months. Evaluated using RECIST v1.1
Time frame: 12 months
Disease Free Survivial (DFS)
Number of participants with DFS. Evaluated using computed tomography (CT).
Time frame: 12 months
Overall Survival (OS)
Number of participants with OS.
Time frame: 12 months
PET response rate after completion of neo-adjuvant therapy.
Evaluated using Positron emission tomography scan \& computed tomography (PET-CT)
Time frame: 10 weeks
Programmed cell death ligand 1 (PD-L1) expression in tumor cells
Change in PD-L1 expression on the surface and in the nucleus of the tumor cells over treatment will be related to complete pathological response (ypCR) by means of logistic regression. Evaluated by immunohistochemistry (IHC). Participants will be evaluated at baseline and reevaluated 2-4 weeks after surgery (for those participants who develop complications from surgery, the revaluation time frame may be extended to 7 weeks).
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Time frame: baseline and between 16-21 weeks