An Open Label Phase 2 Study of Total Neoadjuvant Therapy (TNT) Consisting of FLOT With Pembrolizumab and Short Radiation for Patients With Locally Advanced Gastroesophageal Junction Adenocarcinoma

NCT07018570 | Recruiting Phase 2

• 1 other identifier: EPOC2301
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the effectiveness of treatment for esophagogastric junction carcinoma, total neoadjuvant therapy (TNT) including pembrolizumab and FLOT is conducted, aiming to choose between surgery or organ preservation treatment strategies.

Conditions

Gastroesophageal Junction (GEJ) Adenocarcinoma

Keywords

Esophagogastric junction carcinoma; Total neoadjuvant therapy; TNT; Radiation; Surgery; Pembrolizumab; FLOT; Chemotherapy; Non-operative management; QOL; Phase II

Outcome Measures

Primary Outcomes (1)

• 3-year event-free survival (EFS) rate

  3 years

Secondary Outcomes (13)

• Organ-sparing survival

  3 years

• Overall survival (OS)

  3 years

• Clinical response rate

  3 years

• Clinical complete response rate

  3 years

• Major pathological response rate (MPR rate)

  3 years

Study Arms (1)

Pembrolizumab plus FLOT, Ratiation

EXPERIMENTAL

Drug: Pembrolizumab; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Levofolinate; Drug: Fluorouracil (5-FU); Radiation: Radiation Therapy

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg will be administered via intravenous infusion over 30 minutes, twice at 21-day intervals.

Pembrolizumab plus FLOT, Ratiation

Docetaxel DRUG

Docetaxel 50 mg/m2 will be administered over 60 minutes.

Pembrolizumab plus FLOT, Ratiation

Oxaliplatin DRUG

Oxaliplatin 85 mg/m2 will be administered over 2 hours.

Pembrolizumab plus FLOT, Ratiation

Levofolinate DRUG

Leucovorin 200 mg/m2 will be administered over 2 hours.

Pembrolizumab plus FLOT, Ratiation

Fluorouracil (5-FU) DRUG

5-FU 2600 mg/m2 will be administered over 24 hours.

Pembrolizumab plus FLOT, Ratiation

Radiation Therapy RADIATION

25Gy (5Gy×5fr)

Pembrolizumab plus FLOT, Ratiation

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed esophagogastric junction adenocarcinoma.
• Patients who are naive to systemic therapy and have esophagogastric junction carcinoma of Siewert Type I to III classified as T: 2-4, N: any, and M: 0 according to the 8th edition of the UICC-TNM classification.
• Patients aged 18 years or older as of the day of informed consent.
• Patients with ECOG Performance Status (PS) 0 or 1.
• Patients whose most recent laboratory values within 14 days before registration meet all of the following criteria (testing on the same day of the week two weeks before the date of registration is acceptable).
• \[1\] Neutrophil count ≥1,500/mm3 \[2\] Hemoglobin ≥9.0 g/dL \[3\] Platelet counts ≥100,000/mm3 \[4\] Total bilirubin ≤1.5 mg/dL \[5\] AST (GOT) ≤100 IU/L \[6\] ALT (GPT) ≤100 IU/L \[7\] Serum creatinine ≤1.5 mg/dL 6) Patients who did not receive blood transfusion within 7 days before registration (ineligible if transfusion was performed on the same day of the week one week before the date of registration).
• )Female patients of childbearing potential who tested negative for pregnancy within 14 days before registration. Male and female patients who have agreed to practice appropriate highly effective contraception with low user dependency during the study and for up to 120 days after discontinuation of the investigational drug.
• )Patients who have given consent to provide samples for biomarker analysis. 9)Patients who have given their own written consent to participate in the study

You may not qualify if:

• Patients with a history of using an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
• Patients with a history of acute coronary syndrome (including myocardial infarction and angina unstable), coronary angioplasty, or stent implantation within 6 months before registration.
• Patients with a history or findings of congestive heart failure of Class II or higher according to the New York Heart Association (NYHA) classification of cardiac function.
• Patient with active double cancers \[simultaneous double cancers and metachronous double cancers with a disease-free interval of ≤2 years. However, carcinoma in situ or lesions equivalent to intramucosal carcinoma judged to have been cured by local treatment shall not be included in active double cancers\].
• Patients with serious (requiring hospitalization) complications (e.g., intestinal paralysis, intestinal obstruction, pulmonary fibrosis, difficult-to-control diabetes mellitus, cardiac failure, myocardial infarction, angina unstable, renal failure, hepatic failure, psychiatric disorder, cerebrovascular disorder).
• Patients with active hepatitis B (HBs antigen positive) or hepatitis C.
• Patients with a history of HIV.
• Patients with complicated interstitial lung disease/pneumonitis or with a history of (non-infectious) interstitial lung disease/pneumonitis requiring steroid administration.
• Patients who received a live vaccine within 30 days before the start of investigational drug administration.
• Patients with concomitant autoimmune disease or a history of chronic or recurrent autoimmune disease.
• Patients who require systemic corticosteroids (except for prophylactic administration for testing or allergic reactions, or temporary use to reduce edema associated with radiotherapy) or immunosuppressive medication, or those who have received any of these treatments within 14 days before registration in this study.
• Patients with unhealed wounds (requiring sutures, antimicrobial administration, and cleaning procedures), ulcers, or fractures.
• Pregnant or lactating patients.
• Patients who are unwilling or unable to comply with the study protocol.
• Patients deemed by the investigator to be ineligible for this study.

Sponsors & Collaborators

• National Cancer Center Hospital East: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

National Cancer Center Hospital East

Kashiwa, Chiba, 277, Japan

RECRUITING

MeSH Terms

Conditions

Adenocarcinoma

Interventions

pembrolizumab; Docetaxel; Oxaliplatin; Leucovorin; Fluorouracil; Radiotherapy

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Therapeutics

Central Study Contacts

Kohei Shitara, MD

CONTACT

+81-4-7133-1111; pemflot-tnt@east.ncc.go.jp

Izuma Nakayama, MD

CONTACT

+81-4-7133-1111; pemflot-tnt@east.ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Gastroenterology and Gastrointestinal Oncology Division

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: June 12, 2025
• Study Start: July 24, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2031
• Last Updated: August 26, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1)