Stomach Adenocarcinoma, Gastro-esophageal Junction Cancer
Conditions
Keywords
radiotherapy, PD-1 inhibitors, chemotherapy, locally advanced, gastrectomy, neoadjuvant, hypofractionated radiotherapy
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.
Interventions
DRUGChemotherapy
CAPOX: Capecitabine 1000 mg/m2 twice a day, days 1-14 and oxaliplatin 130 mg/m2, day 1, every 3 weeks
RADIATIONHFRT targeted to the primary lesion and positive lymph nodes
Hypofractionated radiotherapy (HFRT) targeted to the primary lesion and positive lymph nodes (4Gy × 6 fractions)
RADIATIONPULSAR targeted to the primary lesion and positive lymph nodes
Irradiation targeted to the primary lesion and positive lymph nodes (6 Gy/1 fraction)
DRUGAnti-PD-1 monoclonal antibody
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.
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.
Sponsors
Fudan University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete regression (pCR) rate | 6 months after the enrollment of the last subject | Proportion of patients who attain pCR after preoperative treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
Other
| Measure | Time frame |
|---|---|
| To study the association between gut microbiota and the efficacy of the protocol therapy | 36 months after the enrollment of the last subject |
| 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 |
Countries
China
Outcome results
None listed