Clinical trial NCT06728657: Preoperative HFRT Verses PULSAR for Locally Advanced GEJ or Proximal Gastric Adenocarcinoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Stomach Adenocarcinoma
Gastro-esophageal Junction Cancer
Keywords: radiotherapy
PD-1 inhibitors
chemotherapy
locally advanced
gastrectomy
neoadjuvant
hypofractionated radiotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2024-12-11
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Pathological complete regression (pCR) rate
timeFrame: 6 months after the enrollment of the last subject
Secondary outcomes:
measure: R0 resection rate
timeFrame: 6 months after the enrollment of the last subject
measure: Objective response rate (ORR)
timeFrame: 6 months after the recruitment of the last subject
measure: Event-free survival (EFS)
timeFrame: 36 months after the enrollment of the last subject
measure: Overall survival (OS)
timeFrame: 36 months after the enrollment of the last subject
measure: Toxicities
timeFrame: From the time of enrollment, assessed up to 28 days after the last dose of study therapy
measure: Surgical morbidity
timeFrame: During or one month after surgery
measure: Surgical mortality
timeFrame: During or one month after surgery
Other outcomes:
measure: 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
timeFrame: 36 months after the recruitment of the last subject
measure: The association of baseline PD-L1 CPS, TMB, MSI/MMR status, and EBER status with the efficacy of the protocol therapy
timeFrame: 36 months after the enrollment of the last subject
measure: To study the association between gut microbiota and the efficacy of the protocol therapy
timeFrame: 36 months after the enrollment of the last subject
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
Study officials:
References: