Hypofractionated Radiotherapy Plus Immunochemotherapy for Neoadjuvant Treatment of Gastroesophageal Junction Adenocarcinoma

NCT07182565 | Recruiting Phase 1

• 1 other identifier: GEJA-nICRT-2025-05
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to investigate the safety and efficacy of HFRT plus neoadjuvant ICT in locally advanced resectable GEJA.

Conditions

Gastroesophageal Junction Adenocarcinoma; Hypofractionated Radiotherapy

Keywords

neoadjuvant therapy; hypofractionated radiotherapy; immunotherapy; chemotherapy; Serplulimab; pCR

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 ≥1/3 of patients in a given dose cohort experience radiotherapy-related dose-limiting toxicities (DLTs) within 90 days, that dose level will be considered intolerable. The dose level immediately below will then be defined as the maximum tolerated dose (MTD). At least six evaluable patients are required in the MTD cohort.

  within 3 months after the HFRT

• pCR rate in Phase II

  pCR rate: The proportion of patients who achieve pathological complete response (pCR), defined as the absence of viable tumor cells on microscopic examination after neoadjuvant therapy.

  approximately 2 weeks after the resection of primary lesion

Secondary Outcomes (6)

• R0 resection rate

  approximately 2 weeks after the resection of primary lesion

• Objective response rate

  From Baseline up to the pre-surgical assessment (performed within 28 days after the last dose of conversion therapy)

• DFS(disease free survival) rate

  Up to 3 years

• OS(overall survival) rate

  Up to 3 years

• Adverse Events (AEs)

  From the first dose through 90 days after the last dose

Study Arms (2)

Intervention Arm (HFRT+nICT)

EXPERIMENTAL

Radiation: hypofractionated radiotherapy; Drug: PD-1 inhibitor; Drug: TS-1

Control Arm (nICT)

ACTIVE COMPARATOR

Drug: PD-1 inhibitor; Drug: TS-1

Interventions

hypofractionated radiotherapy RADIATION

In Phase Ib, hypofractionated radiotherapy (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+nICT)

PD-1 inhibitor DRUG

Serplulimab will be administered concurrently with chemotherapy at a fixed dose of 300 mg via intravenous infusion on Day 1 of each 3-week cycle.

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

TS-1 DRUG

The TS regimen includes paclitaxel at a dose of 175 mg/m² administered via intravenous infusion on Day 1, and oral administration of tegafur-gimeracil-oteracil (S-1) for 14 consecutive days followed by a 7-day rest period (21-day cycle). The S-1 dose is based on body surface area (BSA): 40 mg twice daily (bid) for BSA ≤ 1.5 m²; 50 mg bid for BSA 1.5-1.6 m²; and 60 mg bid for BSA ≥ 1.6 m².

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

Eligibility Criteria

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

You may qualify if:

• Histologically and/or cytologically confirmed diagnosis of locally advanced adenocarcinoma of the gastroesophageal junction (GEJ) (Siewert types I-III), defined as cT3-4, any N, M0 or cT2 N+, M0 according to the 8th edition of the AJCC staging system.
• Determined as resectable locally advanced disease after multidisciplinary team (MDT) evaluation.
• Age ≥18 years, regardless of sex.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated life expectancy ≥3 months.
• No prior anti-cancer treatment.
• At least one measurable lesion as defined by RECIST v1.1 (lesion diameter ≥1 cm on spiral CT or ≥2 cm on standard CT or MRI), assessed within 28 days prior to enrollment.
• Adequate organ function within 14 days prior to treatment, defined as follows (note: blood transfusions, platelet infusions, or G-CSF use not permitted within 14 days prior to hematologic assessment):
• \) Hematological: Hemoglobin ≥9 g/dL (without recent transfusion); ANC ≥1.5 × 10⁹/L; WBC ≥3.0 × 10⁹/L (no G-CSF use); Platelets ≥75 × 10⁹/L (no IL-11 or TPO use).
• \) Biochemistry: Total bilirubin ≤1.5 × ULN; AST and ALT ≤2.5 × ULN; Serum creatinine ≤1.5 × ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault formula); Serum albumin ≥25 g/L.
• \) Coagulation: INR \<1.5, APTT \<1.5 × ULN within 7 days before enrollment; PT ≤1.5 × ULN.
• Patients with active hepatitis B or C infection must have received antiviral therapy ≥14 days prior to enrollment, with HBV DNA ≤500 IU/mL or 2500 copies/mL, HCV RNA undetectable, and agree to continue antiviral therapy during the study.
• LVEF ≥50% on echocardiography. 11.Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to enrollment and agree to use effective contraception during the study and for at least 3 months after the last dose. Males must use effective contraception during and for at least 3 months after treatment. Female participants must not be breastfeeding or donate/retrieve ova within 60 days after the last dose.
• Willing and able to provide written informed consent and comply with study procedures.

You may not qualify if:

• Confirmed dMMR or MSI-H by immunohistochemistry or genetic testing.
• Evidence of peritoneal or visceral metastasis (based on thoracoabdominal CT, bone scan, or MRI if bone metastasis is suspected).
• Other malignancies within the past 5 years, except cured basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• Known allergy or hypersensitivity to any study drugs or their excipients; contraindications to study drugs.
• Clinically significant upper gastrointestinal bleeding within 30 days before enrollment or randomization.
• Interstitial lung disease, pulmonary fibrosis, active tuberculosis, or steroid-requiring pneumonitis confirmed by CT.
• Active autoimmune or inflammatory disease requiring immunosuppressants within 2 years (e.g., IBD, SLE, sarcoidosis, Wegener's, MG, Graves', rheumatoid arthritis, etc.); exceptions: well-controlled type 1 diabetes, hypothyroidism under hormone replacement, untreated localized skin diseases (e.g., vitiligo, psoriasis).
• Immunodeficiency, history of HIV infection or organ transplantation.
• Active HBV (HBsAg positive) or HCV infection. Previously treated or well-controlled HBV/HCV is allowed.
• Systemic corticosteroids or immunosuppressants within 2 weeks prior to treatment. Exceptions: inhaled or local steroids, adrenal replacement (\<10 mg/day prednisone equivalent), or short-term corticosteroids (\<7 days) for prophylaxis or non-autoimmune indications.
• Uncontrolled comorbidities, including:
• ）Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥100 mmHg); 2）Grade II+ myocardial ischemia or MI within 6 months, arrhythmia (QT ≥480 ms, AF), uncontrolled angina, CHF (NYHA III-IV), valvular disease, cardiomyopathy, stroke or TIA history; 3）Active or uncontrolled infection; 4）Liver disease (cirrhosis, decompensation, active hepatitis); 5）Poorly controlled diabetes (FBG \>10 mmol/L); 6）Proteinuria ≥++ or 24h urine protein \>1.0 g. 12.Coagulation abnormalities (INR \>1.5 or APTT \>1.5 × ULN), known bleeding tendency, or patients receiving thrombolytic or anticoagulant therapy. Known congenital or acquired bleeding or thrombotic disorders, such as hemophilia, coagulation defects, thrombocytopenia, hypersplenism, etc.
• Patients with significant hemoptysis (≥2.5 mL per day), or a history of clinically significant bleeding (e.g., gastrointestinal bleeding, hemorrhagic gastric ulcers, or fecal occult blood test ≥++) within 3 months prior to enrollment.
• Patients requiring long-term anticoagulation with warfarin or heparin, or long-term antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day).
• Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to first dose, or expected to undergo major surgery during the study, or non-diagnostic surgery within 4 weeks prior to trial initiation.

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; titanium silicide

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: September 19, 2025
• Study Start: November 18, 2025
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: January 6, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Sharing period is 5 years, which start from one year after primary outcome publication.
• Access Criteria: Shared for: scientific research institutions, academic journal editors, government agencies Sharing conditions: IPD sharing shall meet the following conditions: Requestor must provide study agreement and relevant ethical review committee approval documents Requestor must ensure legality of data use and privacy protection Requestor must agree to data sharing, and the study team has the right to review the Requestor 's study plan and provide necessary support and interpretation of data

Locations

CN (4)