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

Обзор

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.

Подробное описание

In Immunochemotherapy before short-term radiation therapy, pembrolizumab 200mg will be intravenously infused at 21-day intervals for 2 doses. FLOT (docetaxel 50 mg/m2, oxaliplatin 85 mg/m2, leucovorin 200mg/m2, 5-FU 2600 mg/m2) will be intravenously infused at 14-day intervals for 2 doses.

Regarding short-term radiotherapy, irradiation will be delivered from day1 to day5, with a dose of 5 Gy per fraction for a total of 25 Gy.

In Immunochemotherapy after short-term radiation therapy, pembrolizumab 200mg will be intravenously infused on day 8. FLOT will be intravenously infused on day 1 and day15.

If CR or Near CR is achieved after the first and second efficacy assessment, pembrolizumab 200mg will be intravenously infused at 21-day intervals for 14 doses and FLOT will be intravenously infused at 14-day intervals for 4 doses as immunochemotherapy as non-operative management (NOM).

If CR or Near CR is not achieved after the first or second efficacy assessment, surgery will be performed. And then pembrolizumab 200mg will be intravenously infused at 21-day intervals for 14 doses and FLOT will be intravenously infused at 14-day intervals for 4 doses as Postoperative adjuvant immunochemotherapy.

Вмешательства

• Препарат Pembrolizumab
  Pembrolizumab 200mg will be administered via intravenous infusion over 30 minutes, twice at 21-day intervals.
• Препарат Docetaxel
  Docetaxel 50 mg/m2 will be administered over 60 minutes.
• Препарат Oxaliplatin
  Oxaliplatin 85 mg/m2 will be administered over 2 hours.
• Препарат Levofolinate
  Leucovorin 200 mg/m2 will be administered over 2 hours.
• Препарат Fluorouracil (5-FU)
  5-FU 2600 mg/m2 will be administered over 24 hours.
• Лучевая терапия Radiation Therapy
  25Gy (5Gy×5fr)

Первичные конечные точки

• 3-year event-free survival (EFS) rate [Срок оценки: 3 years]

Вторичные конечные точки (12)

• Organ-sparing survival [Срок оценки: 3 years]
• Overall survival (OS) [Срок оценки: 3 years]
• Clinical response rate [Срок оценки: 3 years]
• Clinical complete response rate [Срок оценки: 3 years]
• Major pathological response rate (MPR rate) [Срок оценки: 3 years]
• Pathological complete response rate (pCR rate) [Срок оценки: 3 years]
• R0 resection rate (R0 rate) [Срок оценки: 3 years]
• TNT completion rate [Срок оценки: 3 years]
• Treatment completion rate [Срок оценки: 3 years]
• Adverse event incidence rate [Срок оценки: 3 years]
• Post-treatment ctDNA clearance [Срок оценки: 3 years]
• EORTC QLQ-C30 [Срок оценки: 3 years]

Критерии участия

<Inclusion Criteria>

• 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).

7)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.

8)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

<Exclusion Criteria>

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Япония · 1 центр

• National Cancer Center Hospital East — Kashiwa

Идентификаторы

NCT: NCT07018570 · EPOC2301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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