Neo-Sequence 1: Neoadjuvant Chemotherapy With or Without Antiangiogenesis and Sequential Immunotherapy for HER2-negative MMR-proficient Locally Advanced Gastric or Gastroesophageal Adenocarcinoma

Completed

• Conditions: Gastric Cancer
• Interventions: Drug: SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody

• Registration Number: NCT05540145
• Lead Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Brief Summary

This is a single-institution, prospective phase II trial designed to evaluate the efficacy of neoadjuvant chemotherapy and sequential immunotherapy in patients with locally advanced esophagogastric junction and gastric adenocarcinoma. Patients with Her-2 positive or dMMR tumors will be excluded from the study. Six cycles of nab-paclitaxel, oxaliplatin and S-1 with or without bevacizumab, followed by three circles of nab-paclitaxel, bevacizumab, with or without S-1 combined with two cycles of PD-1 monoclonal antibody, will be administered as neoadjuvant therapy. Patients will receive different adjuvant treatments depending on the degrees of surgical radicality and the pathological reactions of tumors.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-05-01
• Study First Submitted: 2022-09-12
• Study First Submitted QC: 2022-09-12
• Study First Posted: 2022-09-14
• Primary Completion: 2023-12-31
• Study Completion: 2023-12-31
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-14
• Last Update Posted: 2024-04-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Be willing and able to provide written (signed) informed consent;

2. Age ≥ 18 years and ≤75 years.

3. Has a pathologic diagnosis of gastroesophageal or gastric adenocarcinoma, mucinous adenocarcinoma or signet ring cell carcinoma.

4. Imaging (CT/ultrasonography of cervical lymph nodes and supraclavicular lymph nodes/ endoscopy and endoscopic ultrasound) confirmed at the stage of cT3/4a NanyM0(AJCC 8th).

5. Confirmed by immunohistochemistry (IHC) staining or genetic and transcriptional profiling detection to meet all of the following conditions:

   1. Her-2-negative was defined as IHC -, IHC 1+ or IHC 2+ and FISH negative;
   2. Mismatch repair-proficient (pMMR).

6. The Eastern Cooperative Oncology Group Performance status (ECOG PS) 0-1;

7. The main organ function meets the following criteria within 7 days before treatment:

   1. Hemoglobin (Hb) level ≥9.0 g/dl.
   2. Neutrophil count (ANC)≥1.5×10^9/L.
   3. Platelet (PLT) ≥100×10^9/L
   4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN.
   5. Serum creatinine (Cr) level ≤1.0×ULN and creatinine clearance ≥60 ml/min.
   6. Total bilirubin(TBIL) level ≤1.5×ULN.

Exclusion Criteria

1. Confirmed at stage IV (AJCC 8th) or unresectable by investigator before enrolling.
2. Patienta have had prior chemotherapy, targeted small molecule therapy, or radiation therapy for the current diagnosis of EGJ cancer or gastric cancer.
3. Patients are allergic to study medication and its ingredients.
4. Patients have experienced or currently have other malignancies within 5 years.
5. Patients have an active infection requiring systemic therapy.
6. Women who are pregnant, breast-feeding or planning to become pregnant during treatment or within 6 months after treatment ends.
7. Patients have a history of psychotropic substance abuse and are unable to quit or have a mental disorder.
8. Patients with other severe acute or chronic conditions that may increase the risk of participation in the study and study treatment, or may interfere with interpretation of study results, and judged by the investigator as not suitable for participation in this clinical trial.
9. Diagnosis of immunodeficiency or active autoimmune disease, receiving or being treated with immunomodulators, systemic steroids or immunosuppressive drugs in the past two years.
10. Patients with gastrointestinal obstruction or uncontrolled bleeding undergo emergency surgery.
11. The proportion of other components in the pathology (such as squamous cell carcinoma, neuroendocrine carcinoma, etc.) exceeds 10%

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody	SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody	SOX: Oxaliplatin+S-1

Primary Outcome Measures

Name	Time	Method
Event-free survival (EFS)	From the recruitment to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years	The time from recruitment to any progression of disease precluding surgery, progression or recurrence of disease after surgery, progression of disease in the absence of surgery, or death from any cause.

Secondary Outcome Measures

Name	Time	Method
Major pathological response	From the date of recruitment to 3 months after all treatment ends	It is defined as residual tumors less than 10% after neoadjuvant systemic therapy according to Mandard grade.
R0 resection rate	From the date of recruitment to 3 months after all treatment ends	Rate of microscopically margin-negative resection
Adverse events	From the date of recruitment to 3 months after all treatment ends	Adverse events (AEs) of neoadjuvant and adjuvant systemic therapy will be graded and documented according to NCI-CTCAE v5.0 and immune-related Adverse Event, irAE from the beginning of treatment to 3 months since the last dosage of treatment. Documentary will include severity, lasting period and occurrence time. Surgery complications will also be documented.
Overall survival(OS)	From the date of recruitment to the date of death from any cause or the date of last follow-up, assessed up to 36 months	The time from recruitment to the date of death for any reason or the date of last follow-up

Trial Locations

Locations (1)

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital; 🇨🇳 Beijing, Beijing, China