Hypofractionated Radiotherapy Combined With Immunochemotherapy for Conversion Treatment of Gastroesophageal Junction Adenocarcinoma

NCT07072351 | Recruiting Phase 1

• 1 other identifier: GEJA-ICRT-2025-05
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to investigate the safety and efficacy of conversion therapy using HFRT combined with ICT in locally advanced or metastatic unresectable GEJA.

Conditions

Gastroesophageal Junction Adenocarcinoma; Hypofractionated Radiotherapy; Immunotherapy; Chemotherapy

Keywords

hypofractionated radiotherapy; immunotherapy; chemotherapy; ORR; conversion therapy; gastroesophageal junction adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability in Phase Ib

  Safety will be assessed based on clinical adverse events, vital signs, and abnormalities in laboratory tests during the study period. Adverse events (AEs) will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. All deaths occurring within 90 days after the first dose of treatment or within 30 days after the last dose will be listed along with the causes of death. Laboratory abnormalities will be categorized according to NCI-CTCAE version 5.0. Maximum Tolerated Dose (MTD): If ≥1 out of 3 patients in a given dose cohort experiences radiotherapy-related dose-limiting toxicity (DLT) within 90 days, that dose level will be considered intolerable. The next lower dose level will be defined as the MTD. The MTD cohort must include at least 6 evaluable patients.

  within 3 months after the HFRT

• ORR rate in Phase II

  Objective Response Rate (ORR):ORR is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) as determined by investigators based on RECIST version 1.1. The initial CR or PR must be confirmed by repeat imaging at least 4 weeks after the first documentation of response.

  approximately 4 weeks after the resection of primary lesion

Secondary Outcomes (6)

• R0 resection rate

  approximately 2 weeks after the resection of primary lesion

• DOR (Duration of Response)

  Up to 3 years

• PFS (Progression-Free Survival)

  Up to 3 years

• OS (Overall Survival)

  Up to 3 years

• Adverse Events (AEs)

  From the first dose through 90 days after the last dose

Study Arms (2)

Intervention Arm (HFRT+ICT)

EXPERIMENTAL

Radiation: hypofractionated radiotherapy; Drug: SOX Chemotherapy; Drug: PD-1 inhibitor

Control Arm (nICT)

ACTIVE COMPARATOR

Drug: SOX Chemotherapy; Drug: PD-1 inhibitor

Interventions

hypofractionated radiotherapy RADIATION

In Phase Ib, HFRT will be administered at one of three dose levels: 3 Gy × 5 fractions, 4 Gy × 5 fractions, or 5 Gy × 5 fractions. The recommended dose determined in Phase Ib will be used in Phase II (delivered as 5 fractions).

Also known as: HFRT, LFRT

Intervention Arm (HFRT+ICT)

SOX Chemotherapy DRUG

SOX chemotherapy regimen: Oxaliplatin 130 mg/m² administered by intravenous infusion on Day 1; S-1 administered orally for 14 consecutive days followed by a 7-day rest period. The dosage of S-1 is based on body surface area (BSA): 40 mg twice daily for BSA ≤1.5 m², 50 mg twice daily for BSA between 1.5-1.6 m², and 60 mg twice daily for BSA ≥1.6 m². Each cycle is repeated every 3 weeks.

Control Arm (nICT); Intervention Arm (HFRT+ICT)

PD-1 inhibitor DRUG

Sintilimab 200 mg administered by intravenous infusion on Day 1 of each 3-week cycle.

Control Arm (nICT); Intervention Arm (HFRT+ICT)

Eligibility Criteria

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

You may qualify if:

• Participants must meet all of the following criteria:
• Histologically and/or cytologically confirmed diagnosis of locally advanced gastroesophageal junction adenocarcinoma (GEJA), Siewert type I-III, with staging of cT3-4, any N, M0 or cT2 N+, M0, according to the AJCC 8th edition.
• Resectable locally advanced disease as determined by multidisciplinary team (MDT) assessment.
• Age ≥18 years, regardless of sex.
• ECOG performance status of 0 or 1.
• Estimated life expectancy of ≥3 months.
• No prior anti-tumor therapy.
• At least one measurable lesion per RECIST v1.1, defined as:
• Lesion ≥1 cm in longest diameter on spiral CT, or
• Lesion ≥2 cm in longest diameter on conventional CT or MRI.
• Imaging must be performed within 28 days prior to enrollment.
• Adequate organ function within 14 days prior to treatment, as defined below (Note: No RBC or platelet transfusion or use of G-CSF within 14 days prior to hematology testing):
• Hematologic:
• Hemoglobin ≥9 g/dL (without transfusion)
• ANC ≥1.5 × 10⁹/L

You may not qualify if:

• Participants who meet any of the following conditions will be excluded:
• Diagnosed as mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) by immunohistochemistry or gene testing.
• Evidence of peritoneal or multi-organ metastatic disease, as confirmed by chest and abdominal CT, bone scan, or MRI (in cases with suspected osseous lesions).
• History of or concurrent other malignancies within the past 5 years, excluding cured basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Known allergy to any component of the investigational drugs, history of severe hypersensitivity, or any contraindication to study drugs.
• Clinically significant upper gastrointestinal bleeding within 30 days prior to enrollment or randomization.
• History of congenital pulmonary fibrosis, drug-induced pneumonitis, active pulmonary tuberculosis, or CT-confirmed active pneumonia; interstitial lung disease requiring steroid treatment.
• Active autoimmune or inflammatory diseases requiring immunosuppressive therapy within 2 years prior to treatment, including but not limited to:
• Inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, diverticulitis),
• Systemic lupus erythematosus,
• Sarcoidosis,
• Tuberculosis,
• Wegener's granulomatosis,
• Myasthenia gravis,
• Graves' disease,

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (4)

West China Xiamen Hospital, Sichuan University

Xiamen, Fujian, China

RECRUITING

The Seventh People's Hospital of Chengdu

Chengdu, Sichuan, 610041, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

West China Shangjin Nanfu Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

MeSH Terms

Interventions

Radiation Dose Hypofractionation; Immune Checkpoint Inhibitors

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Yaqin Zhao Associate Chief Physician

CONTACT

+86 18628260828; zhaoyaqin@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: July 9, 2025
• First Posted: July 18, 2025
• Study Start: September 15, 2025
• Primary Completion (Estimated): May 14, 2028
• Study Completion (Estimated): May 14, 2028
• Last Updated: November 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (4)