Preoperative HFRT Verses PULSAR for Locally Advanced GEJ or Proximal Gastric Adenocarcinoma (TORCH-G)

Fudan University

Status and phase: Suspended; Phase 2

Conditions: Gastro-esophageal Junction Cancer; Stomach Adenocarcinoma

Treatments: Drug: Chemotherapy; Drug: Anti-PD-1 monoclonal antibody; Radiation: PULSAR targeted to the primary lesion and positive lymph nodes; Procedure: R0 total/subtotal gastrectomy with D2 lymphadenectomy; Radiation: HFRT targeted to the primary lesion and positive lymph nodes

Study type: Interventional

Funder types: Other

Identifiers

NCT06728657

FDRT-2024-251-3805

Details and patient eligibility

About

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.

Enrollment: 68 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

68 participants in 2 patient groups

HFRT

Experimental group

Description:

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.

Treatment:

Radiation: HFRT targeted to the primary lesion and positive lymph nodes

Procedure: R0 total/subtotal gastrectomy with D2 lymphadenectomy

Drug: Anti-PD-1 monoclonal antibody

Drug: Chemotherapy

PULSAR

Experimental group

Description:

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.

Treatment:

Procedure: R0 total/subtotal gastrectomy with D2 lymphadenectomy

Drug: Anti-PD-1 monoclonal antibody

Radiation: PULSAR targeted to the primary lesion and positive lymph nodes

Drug: Chemotherapy