A Phase II Randomized Trial of Preoperative Hypofractionated Radiotherapy (HFRT) Compared to Personalized Hyperfractionated Stereotactic Adaptive Radiotherapy (PULSAR), Combined With Chemotherapy and PD-1 Monoclonal Antibody for Locally Advanced Gastroesophageal Junction/Proximal Gastric Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- HFRT targeted to the primary lesion and positive lymph nodes
- Conditions
- Stomach Adenocarcinoma
- Sponsor
- Fudan University
- Enrollment
- 68
- Locations
- 1
- Primary Endpoint
- Pathological complete regression (pCR) rate
- Status
- Suspended
- Last Updated
- 10 months ago
Overview
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:
- If the multimodal treatment will improve the pCR rate.
- If the multimodal treatment can be performed safely.
- 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.
Investigators
Zhen Zhang
Professor, Chief Physician, Head of Department of Radiation Oncology, Fudan University Shanghai Cancer Center
Fudan University
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 cT4bNanyM
- •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
- •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.
Arms & Interventions
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.
Intervention: HFRT targeted to the primary lesion and positive lymph nodes
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.
Intervention: Anti-PD-1 monoclonal antibody
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.
Intervention: Chemotherapy
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.
Intervention: R0 total/subtotal gastrectomy with D2 lymphadenectomy
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.
Intervention: PULSAR targeted to the primary lesion and positive lymph nodes
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.
Intervention: Anti-PD-1 monoclonal antibody
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.
Intervention: Chemotherapy
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.
Intervention: R0 total/subtotal gastrectomy with D2 lymphadenectomy
Outcomes
Primary Outcomes
Pathological complete regression (pCR) rate
Time Frame: 6 months after the enrollment of the last subject
Proportion of patients who attain pCR after preoperative treatment.
Secondary Outcomes
- 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)
- Surgical morbidity(During or one month after surgery)
- Surgical mortality(During or one month after surgery)