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

Phase 2

Recruiting

• Conditions: Stomach Adenocarcinoma; Gastro-esophageal Junction Cancer
• Interventions: Radiation: HFRT targeted to the primary lesion and positive lymph nodes; Radiation: PULSAR targeted to the primary lesion and positive lymph nodes; Drug: Anti-PD-1 monoclonal antibody; Drug: Chemotherapy; Procedure: R0 total/subtotal gastrectomy with D2 lymphadenectomy

• Registration Number: NCT06728657
• Lead Sponsor: Fudan University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-01
• Status Verified: 2024-12
• Study First Submitted: 2024-12-01
• Study First Submitted QC: 2024-12-08
• Last Update Submitted: 2024-12-08
• Study First Posted: 2024-12-11
• Last Update Posted: 2024-12-11
• Primary Completion: 2025-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 68

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HFRT	HFRT targeted to the primary lesion and positive lymph nodes	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.
HFRT	Anti-PD-1 monoclonal antibody	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.
HFRT	Chemotherapy	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.
HFRT	R0 total/subtotal gastrectomy with D2 lymphadenectomy	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.
PULSAR	PULSAR targeted to the primary lesion and positive lymph nodes	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.
PULSAR	Anti-PD-1 monoclonal antibody	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.
PULSAR	Chemotherapy	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.
PULSAR	R0 total/subtotal gastrectomy with D2 lymphadenectomy	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.

Primary Outcome Measures

Name	Time	Method
Pathological complete regression (pCR) rate	6 months after the enrollment of the last subject	Proportion of patients who attain pCR after preoperative treatment.

Secondary Outcome Measures

Name	Time	Method
R0 resection rate	6 months after the enrollment of the last subject	Proportion of patients who achieve R0 resection.
Objective response rate (ORR)	6 months after the recruitment of the last subject	Proportion of patients with complete response (CR) or partial response (PR) to preoperative therapy. ORR will be evaluated using RESIST1.1
Event-free survival (EFS)	36 months after the enrollment of the last subject	EFS is defined as the time interval from enrollment to an event which includes disease progression, discontinuation of the treatment for any reason, or death.
Overall survival (OS)	36 months after the enrollment of the last subject	OS is defined as the time interval from enrollment to death of any reason or censoring.
Toxicities	From the time of enrollment, assessed up to 28 days after the last dose of study therapy	Number of participants with treatment-related adverse events (TrAEs) reported between the first dose and 28 days after the last dose of study therapy as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Surgical morbidity	During or one month after surgery	Surgery related adverse events (SRAEs) refer to complications which happen during or one month after surgery. Severe complications after surgery will be documented and classified by Clavien-Dindo classification, such as abdominal or GI tract bleeding, anastomotic fistula, pancreatic fistula of grade B or above, and incision complications (infection, bleeding, rupture).
Surgical mortality	During or one month after surgery	Death from any cause within 30 days of the date of surgery will be considered a surgical mortality death.

Trial Locations

Locations (1)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China