Efficacy of Perioperative Chemotherapy Plus PD-1 Antibody in the Locally Advanced Gastric Cancer

NCT04250948 | Unknown Phase 2

• 1 other identifier: Neoadjuvant PD-1/LAGC
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

For locally advanced gastric cancer (cT3-4aN+M0), neoadjuvant chemotherapy can downstage T and N stage, increase the resectability of tumor, and finally improve the long-term survival. Combination of perioperative PD-1 antibody and chemotherapy for locally advanced gastric cancer could be a novel therapy to increase response rate and resectability and reduce recurrence rate. JS001 in this study is a Chinese anti-PD-1 monoclonal antibody for injection which has been approved for melanoma. This study is a multi-center, open-label, randomized phase II clinical trial to evaluate tolerability, safety and efficacy of JS001 in combination with perioperative chemotherapy in locally advanced gastric cancer.

Conditions

Gastric Cancer; Locally Advanced Solid Tumor

Keywords

Perioperative Therapy; PD-1 antibody; Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• TRG0/1

  Pathological tumor regression grade 0/1

  From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.

Secondary Outcomes (6)

• pCR

  From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.

• R0 resection rate

  From the initiation date of first cycle (each cycle is 21 days) to the date of operation, an average of 12 weeks.

• Recurrence free survival (RFS)

  From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

• Objective response rate (ORR)

  From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

• Disease control rate (DCR)

  From the initiation date of first cycle (each cycle is 21 days) to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years]

Study Arms (2)

XELOX or SOX

ACTIVE COMPARATOR

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1 Oxaliplatin: 130mg/m2, iv drip for 2h, d1, q3w; S-1:40\~60mg Bid, d1\~14, q3w; Capecitabine: 1000mg/m2 Bid, d1-14, q3w; Neoadjuvant chemotherapy for 3 cycles, adjuvant chemotherapy for 5 cycles.

Drug: Oxaliplatin; Drug: S1; Drug: Capecitabine

JS001+XELOX or SOX

EXPERIMENTAL

XELOX: Oxaliplatin+Capecitabine; SOX: Oxaliplatin+S-1 JS001: 240mg, ivdrip, d1, q3w; S-1:40\~60mg Bid, d1\~14, q3w; Capecitabine: 1000mg/m2 Bid, d1-14, q3w; Neoadjuvant chemotherapy for 3 cycles, adjuvant chemotherapy for 5 cycles.

Drug: JS001; Drug: Oxaliplatin; Drug: S1; Drug: Capecitabine

Interventions

JS001 DRUG

JS001, recombinant humanized anti-PD-1 monoclonal antibody for injection; 240mg ivdrip, d1, q3w.

Also known as: PD-1 antibody

JS001+XELOX or SOX

Oxaliplatin DRUG

Oxaliplatin: 130mg/m2，iv drip for 2h，d1, q3w

JS001+XELOX or SOX; XELOX or SOX

S1 DRUG

S-1: 40\~60mg Bid，d1\~14, q3w

JS001+XELOX or SOX; XELOX or SOX

Capecitabine DRUG

Capecitabine: 1000mg/m2 Bid，d1-14, q3w

Also known as: XELODA

JS001+XELOX or SOX; XELOX or SOX

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written (signed) informed consent;
• Histologically CT/MRI confirmed cT3-4aN+M0 gastric adenocarcinoma;
• Consent to send tumor tissue from biopsy or resection for PD-L1, EBV, MSI detection;
• Female or male, 18-75 years;
• ECOG 0-1, no surgery contraindications;
• Physical condition and adequate organ function to ensure the success of abdominal surgery;
• Expected survival ≥3 months;
• Adequate hematological, liver, renal and coagulation function;
• \) Platelet (PLT) count ≥100,000 /mm3; 2) Neutrophil count (ANC) ≥1,500 /mm3; 3) Hemoglobin (Hb) level ≥9.0 g/dl; 4) International normalized ratio (INR) ≤1.5; 5) Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN; 6) Glycosylated hemoglobin (HbA1c) \<7.5%; 7) Total bilirubin (TBIL) level ≤1.5×ULN; 8) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 9) Alkaline phosphatase level ≤2.5×ULN (≤5×ULN in case of liver metastasis); 10) Serum creatinine (Cr) level ≤1.5×ULN and creatinine clearance ≥60 ml/min; 11) Thyroid stimulating hormone (TSH) ≤ULN; 12) Normal serum free thyroid hormone (T4); 13) Normal serum free triiodothyronine (T3); 14) Serum amylase ≤1.5×ULN; 15) Lipase ≤1.5×ULN.
• Females of child bearing age must have a negative pregnancy test, and have to take contraception measures and avoid breast feeding during the study and for 3 months after the last dose; male subjects must agree to taken contraception measures during the study and for 3 months after the last dose.

You may not qualify if:

• Known allergy to study drug or excipients, or allergy to similar drugs;
• Patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured localized tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical or breast carcinoma in situ;
• Uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment;
• Weight loss \>20% within 2 weeks before recruitment;
• Unable to swallow study drug;
• Prior chemotherapy, radiotherapy, surgery for gastric cancer;
• Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent;
• Prior therapy with tyrosine kinase inhibitor within 2 weeks.
• Concurrent medical condition requiring the use of cortisol (\>10mg/day Prednisone or equivalent dose) or other systematic immunosuppressive medications within 14 days before the study treatment. Except: inhalation or topical corticosteroids. Doses \> 10 mg/day prednisone or equivalent for replacement therapy;
• Have vaccination with attenuated live vaccines within 4 weeks prior to initiation of the study treatment or plan to vaccinate during the study;
• Poorly controlled hypertension or diabetes;
• With bleeding tendency, or evident hemoptysis or other hemorrhagic events (e.g. gastrointestinal hemorrhage, hemorrhagic gastric ulcer) within 2 months prior to initiation of study treatment, or presence of hereditary or acquired bleeding or thrombotic tendency (e.g. hemophilia, coagulopathy, thrombocytopenia, etc.), or current/long-term thrombolytic or anticoagulant therapy (except aspirin ≤100 mg/day);
• Present or history of any autoimmune disease;
• With active tuberculosis or receiving previous anti-tuberculosis therapy within one year;
• Diagnosed with interstitial pneumonia, non-infectious pneumonia, pulmonary fibrosis, acute lung disease;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Yuan SQ, Nie RC, Jin Y, Liang CC, Li YF, Jian R, Sun XW, Chen YB, Guan WL, Wang ZX, Qiu HB, Wang W, Chen S, Zhang DS, Ling YH, Xi SY, Cai MY, Huang CY, Yang QX, Liu ZM, Guan YX, Chen YM, Li JB, Tang XW, Peng JS, Zhou ZW, Xu RH, Wang F. Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial. Nat Med. 2024 Feb;30(2):552-559. doi: 10.1038/s41591-023-02721-w. Epub 2024 Jan 2.

  PMID: 38167937 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

spartalizumab; Oxaliplatin; S 1 (combination); Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Rui-hua Xu, MD,PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President, Professor

Study Record Dates

• First Submitted: November 10, 2019
• First Posted: January 31, 2020
• Study Start: October 12, 2019
• Primary Completion: June 27, 2022
• Study Completion: October 5, 2024
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)