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

Phase 2

Recruiting

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

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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Pembrolizumab plus FLOT, Ratiation	Pembrolizumab	-
Pembrolizumab plus FLOT, Ratiation	Docetaxel	-
Pembrolizumab plus FLOT, Ratiation	Oxaliplatin	-
Pembrolizumab plus FLOT, Ratiation	Levofolinate	-
Pembrolizumab plus FLOT, Ratiation	Fluorouracil (5-FU)	-
Pembrolizumab plus FLOT, Ratiation	Radiation Therapy	-

Primary Outcome Measures

Name	Time	Method
3-year event-free survival (EFS) rate	3 years

Secondary Outcome Measures

Name	Time	Method
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
Pathological complete response rate (pCR rate)	3 years
R0 resection rate (R0 rate)	3 years
TNT completion rate	3 years
Treatment completion rate	3 years
Adverse event incidence rate	3 years
Post-treatment ctDNA clearance	3 years
EORTC QLQ-C30	3 years	We are reporting scores from the EORTC QLQ-C30 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30). The scores were transformed to a 0-100 scale following the official EORTC scoring manual. For functional scales and global health status, higher scores indicate a better outcome. For symptom scales/items, higher scores indicate a worse outcome.
EORTC QLQ-OG25	3 years	We are reporting scores from the EORTC QLQ-OG25 (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Oesophago-Gastric module). The scores were transformed to a 0-100 scale following the official EORTC scoring manual. All scales and single items in the QLQ-OG25 are symptom-based. Therefore, higher scores indicate worse symptoms or poorer quality of life.

Locations (1): National Cancer Center Hospital East
🇯🇵
Kashiwa, Chiba, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
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