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

NCT06728657 | Suspended Phase 2 FDA Drug

• 1 other identifier: FDRT-2024-251-3805
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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. 1.If the multimodal treatment will improve the pCR rate.
2. 2.If the multimodal treatment can be performed safely.
3. 3.Hypofractionated radiotherapy (HFRT) or personalized hyperfractionated stereotactic adaptive radiotherapy (PULSAR), which pattern of radiotherapy can better synergize with immunotherapy.

Conditions

Stomach Adenocarcinoma; Gastro-esophageal Junction Cancer

Keywords

radiotherapy; PD-1 inhibitors; chemotherapy; locally advanced; gastrectomy; neoadjuvant; hypofractionated radiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete regression (pCR) rate

  Proportion of patients who attain pCR after preoperative treatment.

  6 months after the enrollment of the last subject

Secondary Outcomes (7)

• R0 resection rate

  6 months after the enrollment of the last subject

• Objective response rate (ORR)

  6 months after the recruitment of the last subject

• Event-free survival (EFS)

  36 months after the enrollment of the last subject

• Overall survival (OS)

  36 months after the enrollment of the last subject

• Toxicities

  From the time of enrollment, assessed up to 28 days after the last dose of study therapy

Other Outcomes (3)

• To measure changes in tumor immune microenvironment (TIME) by single-cell sequencing before and after protocol therapy and correlate with the efficacy of the protocol therapy

  36 months after the recruitment of the last subject

• The association of baseline PD-L1 CPS, TMB, MSI/MMR status, and EBER status with the efficacy of the protocol therapy

  36 months after the enrollment of the last subject

• To study the association between gut microbiota and the efficacy of the protocol therapy

  36 months after the enrollment of the last subject

Study Arms (2)

HFRT

EXPERIMENTAL

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.

Radiation: HFRT 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

PULSAR

EXPERIMENTAL

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.

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

Interventions

HFRT targeted to the primary lesion and positive lymph nodes RADIATION

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

HFRT

PULSAR targeted to the primary lesion and positive lymph nodes RADIATION

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

PULSAR

Anti-PD-1 monoclonal antibody 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.

HFRT; PULSAR

Chemotherapy DRUG

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

HFRT; PULSAR

R0 total/subtotal gastrectomy with D2 lymphadenectomy 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.

HFRT; PULSAR

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically confirmed adenocarcinoma of proximal stomach (G) or gastroesophageal junction (GEJ) (excluding Siewert type I).
• Potentially resectable, cT3-4aN+M0 or cT4bNanyM0.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, 200032, China

Location

MeSH Terms

Interventions

spartalizumab; Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician, Head of Department of Radiation Oncology, Fudan University Shanghai Cancer Center

Study Record Dates

• First Submitted: December 1, 2024
• First Posted: December 11, 2024
• Study Start: July 1, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 18, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)