Perioperative mFOLFOX Plus Pembrolizumab in Gastroesophageal Junction (GEJ) and Stomach Adenocarcinoma
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|ClinicalTrials.gov Identifier: NCT03488667|
Recruitment Status : Recruiting
First Posted : April 5, 2018
Last Update Posted : April 19, 2021
|Condition or disease||Intervention/treatment||Phase|
|Gastro Esophageal Junction Cancer Stomach Cancer Adenocarcinoma||Drug: Neoadjuvant Treatment - mFOLFOX6 & Pembrolizumab Drug: Adjuvant Treatment - mFOLFOX & Pembrolizumab||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Perioperative mFOLFOX (Fluorouracil, Leucovorin, and Oxaliplatin) Chemotherapy Plus Pembrolizumab(MK-3475) Combination in Patients With Potentially Resectable Adenocarcinoma of the Gastroesophageal Junction (GEJ) and Stomach (MISP #52216)|
|Actual Study Start Date :||June 27, 2018|
|Estimated Primary Completion Date :||April 30, 2022|
|Estimated Study Completion Date :||April 30, 2023|
Experimental: mFOLFOX6 (Leucovorin-Fluorouracil-Oxaliplatin) + Pembrolizumab
Drug: Pembrolizumab Dose: 200 mg Dose Frequency: Every three weeks (Q3W) Route: Intravenous (IV) infusion
Drug: Oxaliplatin Dose: 85 milligrams per meter squared (mg/m2) Dose Frequency: Every 2 weeks (Q2W) Route: IV infusion
Drug: Leucovorin Dose: 400 mg/m2 Dose Frequency: Q2W Route: IV infusion
Drug: Fluorouracil Dose: 400 mg/m2 Dose Frequency: Q2W Route: IV bolus
Drug: Fluorouracil Dose: 2,400 mg/m2 Dose Frequency: Q2W Route: IV continuous 46-hour infusion
Pembrolizumab will be administered at a fixed dose of 200 mg IV over 30 minutes every 3 weeks. Participants will receive 3 doses of the drug on Days 1, 22, 43 during the neoadjuvant phase of the study, and 12 doses of the drug on Days 1, 22, 43 during the adjuvant phase of the study (total 15 doses). Participants will receive 4 doses of mFOLFOX6 regimen on Days 1, 15, 29, 43 during the neoadjuvant phase of the study, and 4 doses during the adjuvant phase of the study (total 8 doses).
Drug: Neoadjuvant Treatment - mFOLFOX6 & Pembrolizumab
Pembrolizumab, mFOLFOX Chemotherapy
Drug: Adjuvant Treatment - mFOLFOX & Pembrolizumab
Pembrolizumab, mFOLFOX Chemotherapy
- Pathological response rate (ypRR) [ Time Frame: 10-14 weeks ]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.
- Number of Adverse Events related to toxicity. [ Time Frame: up to 14 months ]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.
- Objective response rate (ORR) [ Time Frame: 12 months ]Number of participants with ORR (partial response and complete response) at 12 months. Evaluated using RECIST v1.1
- Disease Free Survivial (DFS) [ Time Frame: 12 months ]Number of participants with DFS. Evaluated using computed tomography (CT).
- Overall Survival (OS) [ Time Frame: 12 months ]Number of participants with OS.
- PET response rate after completion of neo-adjuvant therapy. [ Time Frame: 10 weeks ]Evaluated using Positron emission tomography scan & computed tomography (PET-CT)
- Programmed cell death ligand 1 (PD-L1) expression in tumor cells [ Time Frame: baseline and between 16-21 weeks ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03488667
|Contact: Kerry Hepler, RNemail@example.com|
|United States, Kansas|
|The University of Kansas Cancer Center||Recruiting|
|Westwood, Kansas, United States, 66205|
|Contact: Kerry Hepler, RN 913-945-7552 firstname.lastname@example.org|
|Principal Investigator:||Weijing Sun, MD, FACP||The University of Kansas - Cancer Center|