Perioperative mFOLFOX Plus Pembrolizumab in Gastroesophageal Junction (GEJ) and Stomach Adenocarcinoma

NCT03488667 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT-2017-PeriopmFOLFOXPem
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gastro Esophageal Junction Cancer; Stomach Cancer; Adenocarcinoma

Keywords

resectable adenocarcinoma of Gastroesophageal Junction; resectable adenocarcinoma of Stomach

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  up to 14 months

Secondary Outcomes (5)

• Objective response rate (ORR)

  12 months

• Disease Free Survivial (DFS)

  12 months

• Overall Survival (OS)

  12 months

• PET response rate after completion of neo-adjuvant therapy.

  10 weeks

• Programmed cell death ligand 1 (PD-L1) expression in tumor cells

  baseline and between 16-21 weeks

Study Arms (1)

mFOLFOX6 (Leucovorin-Fluorouracil-Oxaliplatin) + Pembrolizumab

EXPERIMENTAL

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; Drug: Adjuvant Treatment - mFOLFOX & Pembrolizumab

Interventions

Neoadjuvant Treatment - mFOLFOX6 & Pembrolizumab DRUG

Pembrolizumab, mFOLFOX Chemotherapy

mFOLFOX6 (Leucovorin-Fluorouracil-Oxaliplatin) + Pembrolizumab

Adjuvant Treatment - mFOLFOX & Pembrolizumab DRUG

Pembrolizumab, mFOLFOX Chemotherapy

mFOLFOX6 (Leucovorin-Fluorouracil-Oxaliplatin) + Pembrolizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are 18 - 75 years of age on the day of signing informed consent with histologically or cytologically confirmed diagnosis of adenocarcinoma of the gastroesophegeal junction (GEJ) or stomach will be enrolled in this study.
• Have newly diagnosed localized or locally advanced, potentially resectable disease without any prior systemic chemotherapy.
• Have no evidence of distant metastases.
• Be eligible and reasonably fit to undergo potentially curative resection
• Male participants:
• A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
• Female participants:
• Female participants of childbearing potential must have a negative serum pregnancy within 72 hours prior to enrollment.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at 120 days after the last dose of study treatment. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
• The participant (or legally authorized representative, if applicable) must be willing and able to provide written informed consent for the trial.
• Have evaluable disease . Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have pre-resection tissue available.
• Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• A WOCBP who has a positive serum pregnancy test within 72 hours prior to enrollment on study.
• Has received prior therapy with an anti-PD-1 (Programmed death-1), anti-PD-L1 (programmed death ligand-1), or anti PD L2 (programmed death ligand-2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study enrollment.
• Has received prior chemotherapy (including investigational agents) for any malignant disorder, thoracic radiation therapy or prior surgical resection of an esophagogastric tumor.
• a. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Has biopsy-proven invasion of tracheobronchial tree or tracheo-esophageal fistula.
• Has distant metastatic disease on imaging or staging laparoscopy at the time of study entry.
• Has a known history of active TB (tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Clinically significant peripheral neuropathy at the time of study entry.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

Sponsors & Collaborators

• University of Kansas Medical Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Related Publications (1)

• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

  PMID: 35623069 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Adenocarcinoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Weijing Sun, MD, FACP

  The University of Kansas - Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2018
• First Posted: April 5, 2018
• Study Start: June 27, 2018
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2025
• Last Updated: May 19, 2023

Record last verified: 2023-05

Locations

US (1)