## Protocol Section
### Identification Module
**NCT ID:** NCT06426654

**Brief Title:** Sintilimab Combined With LDRT for Neoadjuvant Treatment of Locally Advanced dMMR/MSI-H Gastric Cancer

**Official Title:** Sintilimab Combined With Low-dose Radiation Therapy for Neoadjuvant Treatment of Locally Advanced Deficient Mismatch Repair/Microsatellite Instability-high Gastric Cancer: a Prospective, Multi-center, Single-arm, Phase Ib/II Clinical Trial

#### Organization Study ID Info
**ID:** WCH242145
#### Organization
**Class:** OTHER
**Full Name:** West China Hospital
### Status Module
#### Completion Date
**Date:** 2027-08-30

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-06-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06-10

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-17
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** West China Hospital

#### Responsible Party

**Investigator Affiliation:** West China Hospital

**Investigator Full Name:** Ming Liu

**Investigator Title:** Clinical Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Recently, growing evidences have suggested that immunotherapy represents a promising treatment option for the neoadjuvant treatment of locally advanced mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastric cancer. In this study, we will explore the efficacy and safety of sintilimab and LDRT in the neoadjuvant treatment for locally advanced dMMR/MSI-H G/GEJ cancer.

**Detailed Description:** This is a prospective, multicenter, single-arm, phase Ib/II trial. In the phase Ib, 4 cases will be enrolled in each treatment group. In the phase II study, a total of 33 patients will be enrolled. Eligible patients will be registered and receive four cycles of sintilimab. Simultaneously, LDRT will be planned and administered. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of sintilimab. The primary endpoint of phase Ib is to determine the optimal radiation dose for phase II study. The primary endpoint of phase II is the pathological complete response (pCR) rate. Secondary endpoints include R0 resection rate, major pathological response (MPR), objective response rate (ORR), 3-year event-free survival (EFS) rate, 3-year overall survival (OS) rate and safety profile of the neoadjuvant regimen.

### Conditions Module

**Conditions:**

- Gastric Cancer

**Keywords:**

- gastric cancer

- neoadjuvant therapy

- sintilimab

- LDRT

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 45

**Type:** ESTIMATED

**Phases:**

- PHASE1

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Laparoscopic exploration is required in all patients to detect occult peritoneal metastases.

All patients will start with one cycle of neoadjuvant therapy of sintilimab: 200 mg, iv drip, d1, q3w.

Then, LDRT will be performed in the target area (including the primary gastric lesion and positive/suspected positive lymph nodes).

After radiotherapy, patients will receive another three cycles of sintilimab. Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of sintilimab.

The adjuvant therapy will start in 4-6 weeks after the surgery, and we recommend adjuvant treatment with sintilimab for up to 10 cycles.

**Intervention Names:**

- Drug: sintiliman plus LDRT

**Label:** sintilimab+LDRT

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- sintilimab+LDRT

**Description:** All patients will start with one cycle of neoadjuvant therapy of sintilimab: sintilimab 200 mg, iv drip, d1, q3w.

LDRT will be performed in the target area. After radiotherapy, patients will receive another three cycles of sintilimab.

Radical D2 gastric cancer resection will be performed 4-6 weeks after the last administration of sintilimab.

The adjuvant therapy will start in 4-6 weeks after the surgery, and we recommend adjuvant treatment with sintilimab for up to 10 cycles.

**Name:** sintiliman plus LDRT

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** defined as the absence of viable tumor cells assessed by histological evaluation criteria after neoadjuvant therapy

**Measure:** pCR rate

**Time Frame:** 5 months after the last subject participating in

#### Secondary Outcomes

**Description:** defined as the rate of the complete surgical removal of any residual cancer cells in the tumor bed

**Measure:** R0 resection rate

**Time Frame:** 5 months after the last subject participating in

**Description:** defined as tumor residual cells ≤10% in the surgical specimen

**Measure:** MPR rate

**Time Frame:** 5 months after the last subject participating in

**Description:** defined as the proportion of patients without event 23 years after enrolment

**Measure:** 3-year event-free survival (DFS)

**Time Frame:** every 3 month postoperation up to 36 months

**Description:** defined as the proportion of patients survived 3 years after enrolment

**Measure:** 2-year OS rate

**Time Frame:** every 3 month postoperation up to 36 months

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Age 18-80 years.
2. Histologically or cytologically confirmed diagnosis of locally advanced G/GEJ adenocarcinoma (cT2N+M0 or cT3-4aNanyM0) as assessed by exploratory laparoscopic surgery, ultrasonography and/or CT/MRI.
3. Resectable G/GEJ cancer, as judged by experienced surgeons.
4. dMMR and/or MSI-H.

4. Eastern Cooperative Oncology Group performance score (ECOG PS) ≤1. 5. Agree to provide blood, feces, and tissue specimens. 6. The expected survival is longer than 6 months. 7. There was no previous antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy, interventional therapy, and other treatments with antitumor effects).

8. Adequate organ and hematological function. 9. Strict contraception. 10. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion Criteria:

1. Unable to comply with the research program or procedures.
2. Undergoing other drug clinical trials or having participated in any drug clinical trials one month before enrollment.
3. Active autoimmune disease or history of refractory autoimmune disease.
4. Receiving corticosteroids (\> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding the following therapies: steroid hormone replacement therapy (≤10mg/d); local steroid therapy; and short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting.
5. Active or clinically significant cardiac disease:

   1. Congestive heart failure \> New York Heart Association (NYHA) class 2;
   2. Active coronary artery disease;
   3. Arrhythmias requiring treatment other than β-blockers or digoxin;
   4. Unstable angina (with angina symptoms at rest), new angina within 3 months before enrollment, or new myocardial infarction within 6 months before enrollment
6. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor was cured and no evidence of disease was found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment.
7. Patients with a history of HIV infection or active hepatitis B/C.
8. Ongoing \> level 2 infection.
9. Symptomatic brain metastasis or meningioma.
10. Unhealed wounds, ulcers or fractures.
11. Renal failure patients requiring blood or peritoneal dialysis.
12. Epileptic that needs medication.
13. Active, symptomatic interstitial pneumonia, pleural or ascites that causes dyspnea (dyspnea ≥ 2 grade).
14. History of organ transplantation (including corneal transplantation).
15. Allergic to research drugs or similar drugs, or suspected allergies.
16. Pregnant or lactating women.
17. The investigator believes that patients who are not suitable for the study.
18. Medical, psychological or social conditions can affect the recruitment of patients and evaluation of study results.
19. Other antitumor therapy (chemotherapy, radiotherapy, surgery, immunotherapy, biotherapy, chemoembolization) other than investigator drugs. Palliative external irradiation for non-target lesions is allowed.
20. Previously used similar immune checkpoint inhibitors.
21. Major surgery 4 weeks before recruitment, open biopsy or major trauma surgery (excluding biliary stents, or percutaneous biliary drainage).
22. Treatment with antitumor Chinese herbal medicine.

**Maximum Age:** 80 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** fly_121988@126.com

**Name:** Pengfei Zhang, M.D

**Phone:** +86-17828163584

**Role:** CONTACT

**Contact 2:**

**Email:** mingliu721@aliyun.com

**Name:** Ming Liu, M.D.

**Phone:** +86-18980606324

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** West China Hospital

**Name:** Kun Yang, M.D.

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000005770

- Term: Gastrointestinal Neoplasms

- ID: D000004067

- Term: Digestive System Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000004066

- Term: Digestive System Diseases

- ID: D000005767

- Term: Gastrointestinal Diseases

- ID: D000013272

- Term: Stomach Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC06

- Name: Digestive System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M16064

- Name: Stomach Neoplasms

- Relevance: HIGH

- As Found: Gastric Cancer

- ID: M27510

- Name: Microsatellite Instability

- Relevance: LOW

- As Found: Unknown

- ID: M8886

- Name: Gastrointestinal Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M7256

- Name: Digestive System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M8883

- Name: Gastrointestinal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M7255

- Name: Digestive System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M16062

- Name: Stomach Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T5486

- Name: Stomach Cancer

- Relevance: HIGH

- As Found: Gastric Cancer

### Condition Browse Module - Meshes

- ID: D000013274

- Term: Stomach Neoplasms

### Misc Info Module

- Version Holder: 2024-05-31
