Preoperative HFRT Verses PULSAR for Locally Advanced GEJ or Proximal Gastric Adenocarcinoma

NCT ID: NCT06728657

Last Updated: 2025-06-18

Basic Information

• Recruitment Status: SUSPENDED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-01
• Study Completion Date: 2028-12-31

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of the multimodal treatment, which includes radiotherapy, chemotherapy and anti-PD-1 immunotherapy. The trial is designed using a pick-the-winner strategy.

The main questions it aims to answer are:

1. If the multimodal treatment will improve the pCR rate.

2. If the multimodal treatment can be performed safely.

3. Hypofractionated radiotherapy (HFRT) or personalized hyperfractionated stereotactic adaptive radiotherapy (PULSAR), which pattern of radiotherapy can better synergize with immunotherapy.

Participants will receive HFRT or PULSAR for the primary lesion and positive lymph nodes, combined with CAPOX and anti-PD-1 immunotherapy. Then, reassessment will be performed within 4 weeks afterwards. For resectable participants, surgical resections will be performed. Postoperative treatment will be determined by the investigators. For unresectable or inoperable participants, the subsequent treatment will be determined by investigators or MDT.

Conditions

Stomach Adenocarcinoma; Gastro-esophageal Junction Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HFRT

Participants will receive upfront hypofractionated radiotherapy (HFRT) of the primary lesion and positive lymph nodes (24 Gy/6 fractions). Afterwards, systemic therapy consisted of CAPOX and PD-1 antibodies will be administered every three weeks, for at least 3 cycles. Then, reassessment will be performed within 4 weeks afterwards. For resectable participants, surgical resections of primary lesion will be performed. Postoperative treatment will be determined by the investigators. For unresectable or inoperable participants, the subsequent treatment will be determined by investigators or MDT.

Group Type: EXPERIMENTAL

HFRT targeted to the primary lesion and positive lymph nodes

Intervention Type: RADIATION

Hypofractionated radiotherapy (HFRT) targeted to the primary lesion and positive lymph nodes (4Gy × 6 fractions)

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

The anti-PD-1 mAb is used on day 1 along with each cycle of chemotherapy. There are no restrictions on the choice of anti-PD-1 mAb. Patients can choose commonly used accessible monoclonal antibodies based on their personal preferences and financial status. The commonly used anti-PD-1 mAb usages are as follows: Nivolumab, 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Sintilimab, 200mg solution intravenously once daily, Q3W.

Chemotherapy

Intervention Type: DRUG

CAPOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks

R0 total/subtotal gastrectomy with D2 lymphadenectomy

Intervention Type: PROCEDURE

For resectable participants, gastrectomy with standard D2 lymphadenectomy is commonly used. The type of gastrectomy performed depends on the location and extent of the primary lesion.

PULSAR

Participants will receive treatment every three weeks, for at least 3 cycles. Each cycle of treatment consists of irradiation (6 Gy/1 fraction) to the primary lesion and positive lymph nodes on day 1, and systemic therapy consisted of CAPOX and PD-1 antibodies will be administered on day 2. Then, reassessment was performed within 4 weeks afterwards. For resectable participants, surgical resections of primary lesion will be performed. Postoperative treatment will be determined by the investigators. For unresectable or inoperable participants, the subsequent treatment will be determined by investigators or MDT.

Group Type: EXPERIMENTAL

PULSAR targeted to the primary lesion and positive lymph nodes

Intervention Type: RADIATION

Irradiation targeted to the primary lesion and positive lymph nodes (6 Gy/1 fraction)

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

The anti-PD-1 mAb is used on day 1 along with each cycle of chemotherapy. There are no restrictions on the choice of anti-PD-1 mAb. Patients can choose commonly used accessible monoclonal antibodies based on their personal preferences and financial status. The commonly used anti-PD-1 mAb usages are as follows: Nivolumab, 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Sintilimab, 200mg solution intravenously once daily, Q3W.

Chemotherapy

Intervention Type: DRUG

CAPOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks

R0 total/subtotal gastrectomy with D2 lymphadenectomy

Intervention Type: PROCEDURE

For resectable participants, gastrectomy with standard D2 lymphadenectomy is commonly used. The type of gastrectomy performed depends on the location and extent of the primary lesion.

Interventions

HFRT targeted to the primary lesion and positive lymph nodes

Hypofractionated radiotherapy (HFRT) targeted to the primary lesion and positive lymph nodes (4Gy × 6 fractions)

Intervention Type: RADIATION

PULSAR targeted to the primary lesion and positive lymph nodes

Irradiation targeted to the primary lesion and positive lymph nodes (6 Gy/1 fraction)

Intervention Type: RADIATION

Anti-PD-1 monoclonal antibody

The anti-PD-1 mAb is used on day 1 along with each cycle of chemotherapy. There are no restrictions on the choice of anti-PD-1 mAb. Patients can choose commonly used accessible monoclonal antibodies based on their personal preferences and financial status. The commonly used anti-PD-1 mAb usages are as follows: Nivolumab, 360mg solution intravenously once daily, Q3W; OR Pembrolizumab/Sintilimab, 200mg solution intravenously once daily, Q3W.

Intervention Type: DRUG

Chemotherapy

CAPOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks

Intervention Type: DRUG

R0 total/subtotal gastrectomy with D2 lymphadenectomy

For resectable participants, gastrectomy with standard D2 lymphadenectomy is commonly used. The type of gastrectomy performed depends on the location and extent of the primary lesion.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Histopathologically confirmed adenocarcinoma of proximal stomach (G) or gastroesophageal junction (GEJ) (excluding Siewert type I).
• Potentially resectable, cT3-4aN+M0 or cT4bNanyM0.
• Exclusion of peritoneal metastasis through laparoscopic exploration or FAPI PET/CT.
• The status of HER2, MMR, EBER is clear.
• Male or female. Patient age ≥ 18 years and ≤ 75 years.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1.
• Physical state or organ function can tolerate the planned treatment of the study protocol.
• No previous surgery or antitumor therapies, including chemotherapy, radiotherapy, or immunotherapy, were administered.
• Patients agree to sign written informed consent before recruitment.

Exclusion Criteria

• Pregnancy or breastfeeding women.
• History of other malignancies within 5 years.
• Serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
• Immunodeficiency disease or long-term using of immunosuppressive agents.
• Allergic to any component of the therapy.
• Any other condition or disease that is not suitable to take the therapy included in the protocol.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Zhen Zhang

Professor, Chief Physician, Head of Department of Radiation Oncology, Fudan University Shanghai Cancer Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Fudan University Shanghai Cancer Center

Shanghai, , China

Countries

China

Other Identifiers

FDRT-2024-251-3805

Identifier Type: -

Identifier Source: org_study_id