Short Course Radiotherapy With Sequential Disitamab Vedotin Combined With S-1 and Sintilimab as Whole Course Neoadjuvant Therapy for HER2 Expressed Locally Progressive Gastric Cancer

NCT ID: NCT06487429

Last Updated: 2024-07-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-08
• Study Completion Date: 2028-05-31

Brief Summary

This study is a prospective, open label, phase II clinical study intended to include patients with locally advanced gastric adenocarcinoma who have not undergone any treatment and are eligible for surgery. The study aims to evaluate the efficacy and safety of the short course sequential radiotherapy regimen of Disitamab Vedotin combined with S-1 and Sintilimab in neoadjuvant therapy for HER2 expressing locally advanced gastric cancer.

Detailed Description

This study is a prospective, open label, phase II clinical study intended to include patients with locally advanced gastric adenocarcinoma who have not undergone any treatment and are eligible for surgery. The study aims to evaluate the efficacy and safety of the short course sequential radiotherapy regimen of Disitamab Vedotin combined with S-1 and Sintilimab in neoadjuvant therapy for HER2 expressing locally advanced gastric cancer.

After signing informed consent and screening to meet the inclusion criteria, the patient received full course neoadjuvant therapy: short course radiotherapy, rest for 1 week, sequential 3 cycles of Disitamab Vedotin combined with S-1 and Sintilimab, and preoperative imaging examination within 3-4 weeks after the last medication to evaluate the efficacy of neoadjuvant therapy and the possibility of curative D2 resection. The decision to undergo adjuvant treatment after radical surgery for gastric cancer is made by the researcher.

Conditions

Gastric Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Short term radiotherapy with continuous use of Disitamab Vedotin, Sintilimab, and S-1

Short range radiotherapy, PCTV (Clinical Plan Target Area) DT 25Gy/5F, once daily for a total of 5 days, continuous irradiation, and IMRT (Intensity Modulated Radiotherapy) technology; After a week of rest, radiotherapy and chemotherapy combined with immunotherapy will be performed

• Disitamab Vedotin: 2.5 mg/kg, intravenous infusion, d1，Q3W；
• Sintilimab: 200mg, iv；
• S-1: 40 mg/dose, oral, bid，d1-14；Q3W

Group Type: EXPERIMENTAL

Short range radiotherapy with sequential Disitamab Vedotin combined with S-1 and xindilizumab

Intervention Type: DRUG

Short range radiotherapy, PCTV (clinical planned target area) DT 25Gy/5F, once a day, for a total of 5 days, continuous irradiation, and IMRT (intensity modulated radiation therapy) technology; After a week of rest, radiotherapy and chemotherapy combined with immunotherapy will be performed

• Disitamab Vedotin: 2.5 mg/kg, intravenous infusion, d1, Q3W;
• Sintilimab: 200mg, iv;
• S-1: 40 mg/dose, oral, bid, d1-14; Q3W Whether to undergo adjuvant therapy after surgery is determined by the researcher

Interventions

Short range radiotherapy with sequential Disitamab Vedotin combined with S-1 and xindilizumab

Short range radiotherapy, PCTV (clinical planned target area) DT 25Gy/5F, once a day, for a total of 5 days, continuous irradiation, and IMRT (intensity modulated radiation therapy) technology; After a week of rest, radiotherapy and chemotherapy combined with immunotherapy will be performed

• Disitamab Vedotin: 2.5 mg/kg, intravenous infusion, d1, Q3W;
• Sintilimab: 200mg, iv;
• S-1: 40 mg/dose, oral, bid, d1-14; Q3W Whether to undergo adjuvant therapy after surgery is determined by the researcher

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 1. The subjects voluntarily joined this study, were able to complete the signing of the informed consent form, and had good compliance; 2. Age range from 18 to 75 years old (when signing the informed consent form), regardless of gender; 3. Gastric cancer or gastroesophageal junction adenocarcinoma confirmed by histology and/or cytology, diagnosed with local progression according to AJCC 8th edition standards, cT3-4N+M0 diagnosed with cTNM based on endoscopic ultrasound or enhanced CT/MRI scanning (combined with diagnostic laparoscopic exploration if necessary), and agreeing to undergo radical surgical treatment. The researcher evaluates the lesion as resectable; 4. Have not received systematic treatment for the current disease in the past, including anti-tumor radiotherapy, chemotherapy, immunotherapy, etc; 5. IHC results confirm HER2 expression (defined as IHC1+, 2+, 3+); 6. ECOG score 0-1 points; 7. Expected survival time ≥ 6 months; 8. The main organs are functioning well; 9. Fertility subjects must use appropriate methods of contraception during the study period and within 120 days after the end of the study. They must have a negative serum pregnancy test within 7 days before enrollment and must be non lactating subjects.

Exclusion Criteria

-1. Diagnosed as malignant diseases other than gastric cancer within 5 years prior to initial administration (excluding curative basal cell carcinoma, squamous cell carcinoma of the skin, and/or curative resection of carcinoma in situ) 2. The tumor lesion has a tendency for bleeding (such as the presence of active ulcer tumor lesions with positive fecal occult blood test, history of vomiting blood or black stools within 2 months before signing the informed consent form, and a risk of gastrointestinal bleeding determined by the researcher), or having received blood transfusion treatment 4 weeks before the study medication; 3. Unable to take medication orally; 4. Currently participating in intervention clinical research treatment, or having received other research drugs or used research instruments within 4 weeks before the first administration; 5. Previously received the following therapies: anti-HER2, anti-PD-1, anti-PD-L1 drugs, anti-PD-L2 drugs, or drugs targeting another stimulus or synergistic inhibition of T cell receptors (including but not limited to CTLA-4, OX-40, CD137, etc.); 6. Have received systematic systemic treatment with traditional Chinese patent medicines and simple preparations with anti-tumor indications or drugs with immunomodulatory effect (including thymosin, interferon, interleukin, except for local use to control pleural effusion) within 2 weeks before the first administration; 7. Active autoimmune diseases that require systemic treatment (such as the use of disease relieving drugs, glucocorticoids, or immunosuppressants) have occurred within 2 years prior to the first administration. Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatments; 8. The study is currently undergoing systemic glucocorticoid therapy (excluding local glucocorticoids through nasal spray, inhalation, or other routes) or any other form of immunosuppressive therapy within 7 days prior to the first administration; Note: Physiological doses of glucocorticoids (≤ 10 mg/day of prednisone or equivalent) are allowed to be used; 9. Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 10. Known individuals who are allergic to the drugs used in this study; 11. Peripheral neuropathy ≥ grade 2; 12. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 13. Active hepatitis B or hepatitis C subjects (HBsAg positive with HBV DNA titers higher than the upper limit of normal; HCVAb positive with HCV RNA titers higher than the upper limit of normal); 14. Have received a live vaccine within 30 days before the first administration (1st cycle, 1st day); Note: It is allowed to receive inactivated viral vaccines for seasonal influenza within 30 days before the first administration; However, it is not allowed to receive attenuated live influenza vaccines administered intranasally.

15. Pregnant or lactating women; 16. Existence of any serious or uncontrollable systemic diseases 17. Medical history or evidence of illness that may interfere with the trial results, hinder the full participation of subjects in the study, abnormal treatment or laboratory test values, or other situations that the researcher deems unsuitable for enrollment. The researcher believes that there are other potential risks that are not suitable for participation in this study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RemeGen Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tao Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Union Hospital affiliated to Tongji Medical College of Huazhong University ofScience and Technology

Locations

Zhang Tao

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tao Zhang, MD

Role: CONTACT

1277577866@qq.com

02785871982

Zhenyu Lin, MD

Role: CONTACT

tojilin@gmail.com

15827130393

Facility Contacts

Tao Zhang, MD

Role: primary

1277577866@qq.com

862785871982

Other Identifiers

RCVDGIIIR015

Identifier Type: -

Identifier Source: org_study_id