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

NCT ID: NCT05540145

Last Updated: 2024-04-16

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-05-01
• Study Completion Date: 2023-12-31

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.

Conditions

Gastric Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody

SOX: Oxaliplatin+S-1

SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody

Intervention Type: DRUG

Drug: Paclitaxel(albumin-bound) 130mg/m2, ivgtt, D1, Q2w Drug: Oxaliplatin 70 mg/m2, ivgtt, D1, q2w Drug: S-1 40mg (body surface area < 1.25m2), bid, D1-8, Q2w 50mg (body surface area >1.25m2, <1.5 m2), bid, D1-8, Q2w 60mg (body surface area >1.5m2), bid, D1-8, Q2w Drug: Bevacizumab, 5mg/kg, ivgtt, D1, Q14d Drug: PD-1 antibody, 200mg, ivgtt, D1, Q21d Patients with Her-2 negative, MMR-proficient locally advanced esophagogastric junction or gastric adenocarcinoma will receive 6 cycles of neoadjuvant chemotherapy with or without antiangiogenesis. After comprehensive evaluations, patients who respond to chemotherapy will further receive 2 cycles of PD-1 antibody comibed with antiangiogenesis and chemotherapy as neoadjuvant therapy.

Drug: Pembrolizumab or sintilimab, 100~200mg, ivgtt, D1, Q3w. Patients will make the final decision of PD -1 antibody according to their economic condition.

Interventions

SOX plus Paclitaxel with or without antiangiogenesis followed by PD-1 antibody

Drug: Paclitaxel(albumin-bound) 130mg/m2, ivgtt, D1, Q2w Drug: Oxaliplatin 70 mg/m2, ivgtt, D1, q2w Drug: S-1 40mg (body surface area < 1.25m2), bid, D1-8, Q2w 50mg (body surface area >1.25m2, <1.5 m2), bid, D1-8, Q2w 60mg (body surface area >1.5m2), bid, D1-8, Q2w Drug: Bevacizumab, 5mg/kg, ivgtt, D1, Q14d Drug: PD-1 antibody, 200mg, ivgtt, D1, Q21d Patients with Her-2 negative, MMR-proficient locally advanced esophagogastric junction or gastric adenocarcinoma will receive 6 cycles of neoadjuvant chemotherapy with or without antiangiogenesis. After comprehensive evaluations, patients who respond to chemotherapy will further receive 2 cycles of PD-1 antibody comibed with antiangiogenesis and chemotherapy as neoadjuvant therapy.

Drug: Pembrolizumab or sintilimab, 100~200mg, ivgtt, D1, Q3w. Patients will make the final decision of PD -1 antibody according to their economic condition.

Intervention Type: DRUG

Eligibility Criteria

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%

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

Sponsors

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: lead

Responsible Party

Dong Bing Zhao

Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

Beijing, Beijing Municipality, China

Countries

China

Other Identifiers

21/489-3160

Identifier Type: -

Identifier Source: org_study_id