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
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 68
- 试验地点
- 1
- 主要终点
- Pathological complete regression (pCR) rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: HFRT targeted to the primary lesion and positive lymph nodes (Radiation)
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.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
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.
干预措施: Chemotherapy (Drug)
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.
干预措施: R0 total/subtotal gastrectomy with D2 lymphadenectomy (Procedure)
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.
干预措施: PULSAR targeted to the primary lesion and positive lymph nodes (Radiation)
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.
干预措施: Anti-PD-1 monoclonal antibody (Drug)
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.
干预措施: Chemotherapy (Drug)
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.
干预措施: R0 total/subtotal gastrectomy with D2 lymphadenectomy (Procedure)
结局指标
主要结局
Pathological complete regression (pCR) rate
时间窗: 6 months after the enrollment of the last subject
Proportion of patients who attain pCR after preoperative treatment.
次要结局
- 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)
研究者
Zhen Zhang
Professor, Chief Physician, Head of Department of Radiation Oncology, Fudan University Shanghai Cancer Center
Fudan University