Neoadjuvant Immunotherapy for Resectable Gastric Cancer

NCT03878472 | Completed Phase 2

• 1 other identifier: NIPASS2019
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Target population: patients with resectable locally advanced gastric cancer (cT3-4bN+M0).
2. 2.Primary objective:
3. 3.To evaluate the imaging objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of PD-1 antibody alone or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant therapy for locally advanced gastric cancer.
4. 4.To evaluate the safety of PD-1 antibody or in combination with apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Pathological remission rate (PRR) rate of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.

  The pathological response was calculated according to the proportion of residual viable tumor cells in the tumor bed. Complete pathological response (CPR) was defined as no residue tumor cells. Major pathological response (MPR) was defined as less than 10% residue tumor cells.

  5 months after the last subject participating in

• Immunotherapy-related biomarkers

  To evaluate the relationship between tumor pathological remission and immunotherapy related biomarkers, including tumor genome, tumor microenvironment and host immune system response biomarkers.

  5 months after the last subject participating in

Secondary Outcomes (5)

• objective response rate (ORR) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.

  Time Frame: 36 months after the last subject participating in

• progression free survival (PFS)of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.

  Time Frame: 36 months after the last subject participating in

• overall survival (OS) of PD-1 antibody monotherapy or in combination with anti-angiogenesis VEGFR2-TKI apatinib ± S1 ± Oxaliplatin in neoadjuvant (preoperative) treatment of resectable locally advanced gastric cancer.

  Time Frame: 36 months after the last subject participating in

• safety as measured by the rate of adverse events (AEs), laboratory abnormalities, dose adjustment, discontinuation of administration, early discontinuation of the study drug, and delay to surgery.

  Time Frame: 1 month after the last date of treatment

• R0 resection rate

  5 months after the last subject participating in

Study Arms (4)

Neoadjuvant immunotherapy with PD-1

EXPERIMENTAL

Drug: SHR1210

Neoadjuvant immunotherapy with PD-1+apatinib

EXPERIMENTAL

Drug: SHR1210; Drug: Apatinib

Neoadjuvant immunotherapy with PD-1+apatinib+S1

EXPERIMENTAL

Drug: SHR1210; Drug: Apatinib; Drug: S1

Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin

EXPERIMENTAL

Drug: SHR1210; Drug: Apatinib; Drug: S1; Drug: Oxaliplatin

Interventions

SHR1210 DRUG

The patients will receive at least two cycles of SHR-1210 (200 mg, invdrip d1) every two weeks and be accessed for operational suitability every two cycles.

Neoadjuvant immunotherapy with PD-1; Neoadjuvant immunotherapy with PD-1+apatinib; Neoadjuvant immunotherapy with PD-1+apatinib+S1; Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin

Apatinib DRUG

The patients will received apatinib (250mg po qd) until 10 ± 2 days before surgery.

Neoadjuvant immunotherapy with PD-1+apatinib; Neoadjuvant immunotherapy with PD-1+apatinib+S1; Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin

S1 DRUG

The patients will received S1 (50 mg/m2, po, bid, d1-d10) every two weeks and be accessed for operational suitability every two cycles.

Neoadjuvant immunotherapy with PD-1+apatinib+S1; Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin

Oxaliplatin DRUG

The patients will receive at least two cycles of oxaliplatin (85 mg/m2 d1) every two weeks and be accessed for operational suitability every two cycles.

Neoadjuvant immunotherapy with PD-1+apatinib+S1+Oxaliplatin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18-70 years old, both genders, histologically documented gastric cancer.
• Newly diagnosed locally advanced, potentially resectable disease without any prior antitumor treatment
• clinically diagnosed stage T3-4bN+M0 according to ultrasound endoscopy or enhanced CT/MRI scan.
• Eligible and reasonably suitable for potentially curative resection
• Written (signed) informed consent.
• Pathological tissue available
• ECOG: 0-1.
• Adequate organ function.
• Willingness to provide blood and tissue samples for research purposes.
• Good compliance with the study procedures, including lab and auxiliary examination and treatment.
• Female patients should not be pregnant or breast feeding.
• Agree to take contraception measures during treatment and in 120 days after last dose of SHR-1210.
• Life expectancy of at least 6 months.

You may not qualify if:

• Patients with distant metastasis.
• History of chemotherapy, radiation, immunotherapy, or radical resection of gastric cancer.
• patients with active autoimmune disease or history of refractory autoimmune disease.
• patients with active malignant tumor in recent 2 years, except the tumor studied in this research or cured locally tumor like resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ.
• uncontrollable pleural effusion, pericardial effusion, or ascites in 2 weeks before recruitment.
• patients who have digestive tract bleeding in 2 weeks before recruitment or with high risk of bleeding.
• perforation / fistula of GI tract in 6 months before recruitment.
• pulmonary disease history: interstitial pulmonary disease, non-infective pneumonitis, pulmonary fibrosis, acute pulmonary disease.
• uncontrollable systemic diseases, including diabetes, hypertension etc.
• severe chronic or active infections in need of systemic antibacterial, antifungal, or antiviral treatment, including TB or HIV, etc.
• patients with untreated chronic hepatitis B or HBV DNA over 500 IU/ml or positive HCV RNA.
• patients with any cardiovascular risk factors below: （1）cardiac chest pain occurring in 28 days before recruitment, defined as moderate pain that limits daily activity.
• （2）pulmonary embolism with symptoms occurring in 28 days before recruitment. （3）acute myocardial infarction occurring in 6 months before recruitment. （4）any history of heart failure reaching grade 3/4 of NYHA in 6 months before recruitment.
• （5）ventricular arrhythmias of Grade 2 or grater in 6 months before recruitment, or accompanied by supraventricular tachyarrhythmias requiring medical treatment.
• （6）cerebrovascular accident within 6 months before recruitment. 14. patients with peripheral neuropathy NCI CTC AE grade 1, except those with only deep tendon reflex disappearing.

Sponsors & Collaborators

• Qilu Hospital of Shandong University: lead

Study Sites (1)

Qilu hospital of Shandong univertisy

Jinan, Shandong, 250012, China

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

camrelizumab; apatinib; S 1 (combination); Oxaliplatin

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 18, 2019
• Study Start: April 1, 2019
• Primary Completion: June 1, 2022
• Study Completion: May 31, 2024
• Last Updated: December 16, 2024

Record last verified: 2021-05

Locations

CN (1)