Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer

• ClinicalTrials.gov Identifier: NCT04592913
• Recruitment Status: Active, not recruiting
• First Posted: October 19, 2020
• Last Update Posted: March 17, 2023
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Tracking Information

• First Submitted Date: August 26, 2020
• First Posted Date: October 19, 2020
• Last Update Posted Date: March 17, 2023
• Actual Study Start Date: November 17, 2020
• Estimated Primary Completion Date: February 14, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2020)

Event-free survival (EFS) [ Time Frame: Up to 5 years ]

EFS is the time from date of randomization until the date of disease progression or death.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 13, 2020)

• To compare Arm A relative to Arm B on overall survival (OS) [ Time Frame: Up to 5 years ]
  Overall survival is length of time from randomization until the date of death due to any cause.
• To compare Arm A relative to Arm B on pathological complete response (pCR) rate [ Time Frame: Up to 5 years ]
  pCR rate is the proportion of patients who have no residual viable tumor in the resected specimens.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessing Durvalumab and FLOT Chemotherapy in Resectable Gastric and Gastroesophageal Junction Cancer
• Official Title: A Randomized, Double-blind, Placebo-controlled, Phase III Study of Neoadjuvant-Adjuvant Durvalumab and FLOT Chemotherapy Followed by Adjuvant Durvalumab in Patients With Resectable Gastric and Gastroesophageal Junction Cancer (GC/GEJC)
• Brief Summary: This is a Global Study of Neoadjuvant-Adjuvant Durvalumab or Placebo and FLOT Chemotherapy Followed by Adjuvant Durvalumab or Placebo in Patients with Resectable Gastric and Gastroesophageal Cancer (GC/GEJC) (MATTERHORN).
• Detailed Description: This study investigates treatment of durvalumab or placebo therapy combined with FLOT chemotherapy (flurouroacil + leucovorin + oxaliplatin + docetaxel) given before surgery (neoadjuvant) and durvalumab or placebo therapy combined with FLOT chemotherapy after surgery (adjuvant), will work and be safe for the treatment of resectable (removable by surgery) gastric or gastroesophageal cancer, and also to better understand the studied disease and associated health problems.
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Randomized, Double-blind, Placebo-controlled study

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Gastrointestinal Neoplasms
• Esophagogastric Junction

Intervention

• Drug: Durvalumab
  Human monoclonal antibody
• Drug: FLOT chemotherapy
  A combination treatment made up of flurouroacil + leucovorin + oxaliplatin + docetaxel

Study Arms

• Placebo Comparator: Arm B
  placebo product and FLOT chemotherapy
  Intervention: Drug: FLOT chemotherapy
• Experimental: Arm A
  Durvalumab and FLOT chemotherapy
  Interventions:

  • Drug: Durvalumab
  • Drug: FLOT chemotherapy

Publications *

• 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.
• Janjigian YY, Van Cutsem E, Muro K, Wainberg Z, Al-Batran SE, Hyung WJ, Molena D, Marcovitz M, Ruscica D, Robbins SH, Negro A, Tabernero J. MATTERHORN: phase III study of durvalumab plus FLOT chemotherapy in resectable gastric/gastroesophageal junction cancer. Future Oncol. 2022 Jun;18(20):2465-2473. doi: 10.2217/fon-2022-0093. Epub 2022 May 10.
• Cowzer D, Janjigian YY. Top advances in esophageal/gastroesophageal junction cancers in 2021. Cancer. 2022 May 15;128(10):1894-1899. doi: 10.1002/cncr.34140. Epub 2022 Feb 18. No abstract available.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 16, 2023): 958
• Original Estimated Enrollment (submitted: October 13, 2020): 900
• Estimated Study Completion Date: February 14, 2025
• Estimated Primary Completion Date: February 14, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Patients with histologically documented gastric or gastroesophageal junction adenocarcinoma with resectable disease (Stage II or higher per AJCC 8th edition).
• Patients must undergo radical surgery.
• No prior anti-cancer therapy for the current malignancy.
• World Health Organization (WHO)/ECOG performance status of 0 or 1 at enrollment.
• Adequate organ and marrow function.
• Availability of tumor sample prior to study entry.
• Must have a life expectancy of at least 24 weeks.

Key Exclusion Criteria:

• Patients with peritoneal dissemination or distant metastasis.
• Patients with adenosquamous cell carcinoma, squamous cell carcinoma, or GI stromal tumor.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.
• Contra-indication to any of the study drugs.
• History of allogeneic organ transplantation.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 200 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Belgium, Brazil, Canada, Chile, Denmark, France, Germany, Hungary, Japan, Korea, Republic of, Netherlands, Peru, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04592913
• Other Study ID Numbers: D910GC00001; 2019-001555-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: AstraZeneca
• Original Responsible Party: Same as current
• Current Study Sponsor: AstraZeneca
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: AstraZeneca
• Verification Date: March 2023