Neoadjuvant Chemoradiation Plus PD-1 Antibody(SHR-1210) in Locally Advanced Proximal Stomach Adenocarcinoma

NCT03631615 | Unknown Phase 2 DMC

• 1 other identifier: SHR-1210-CRT-GC-IIT
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.Target population: patients with resectable locally advanced proximal (including gastroesophageal junction, fundus and upper body) stomach adenocarcinoma (cT3-4aN+M0).
2. 2.Primary objective: pathological complete remission (pCR) rate of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210) in patients with locally advanced proximal stomach adenocarcinoma.
3. 3.pathological remission rate (pRR) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)
4. 4.objective response rate (ORR) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)
5. 5.progression free survival (PFS)/ overall survival (OS) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)
6. 6.safety of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)
7. 7.induction chemotherapy (3w): one cycle of XELOX regimen (capecitabine 1000 mg/m2 bid\*14d + oxaliplatin 130mg/m2, d1, Q21d);
8. 8.within one week after the induction, concurrent chemoradiation will be started (5w): intensity modulated radiotherapy was given for tumors and high-risk lymphatic drainage areas, total dose:45Gy/25d, 1.8Gy/d, capecitabine (850 mg/m2, bid, po) will be given during radiotherapy as sensitizer.
9. 9.consolidation chemotherapy will be started in 2-3w after concurrent chemoradiation: one cycle of XELOX regimen (capecitabine 1000 mg/m2 bid\*14d + oxaliplatin 130mg/m2, d1, Q21d); From the beginning of induction chemo to 3w before surgery, PD-1 antibody SHR-1210 will be given（200mg, iv, q3w).

Conditions

Gastric Adenocarcinoma

Keywords

neoadjuvant chemoradiation; PD-1 antibody(SHR-1210); locally advanced proximal stomach adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• pathological complete remission (pCR) rate of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210) in patients with locally advanced proximal stomach adenocarcinoma.

  rate of patients with no residual tumor lesion (Grade 3) in surgical specimen

  5 months after the last subject participating in

Secondary Outcomes (5)

• pathological remission rate (pRR) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

  5 months after the last subject participating in

• objective response rate (ORR) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

  36 months after the last subject participating in

• progression free survival (PFS) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

  36 months after the last subject participating in

• overall survival (OS) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

  36 months after the last subject participating in

• safety of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

  1 month after the last date of treatment

Study Arms (1)

Neoadjuvant therpy

EXPERIMENTAL

neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

Drug: Neoadjuvant chemoradiation plus PD-1 antibody(SHR-1210)

Interventions

Neoadjuvant chemoradiation plus PD-1 antibody(SHR-1210) DRUG

Patients will be given the perioperative treatment as below once recruited: 1. induction Neochemotherapy (3w): one cycle of XELOX regimen before surgery; 2. within one week after the induction, concurrent neochemoradiation will be started (5w): intensity modulated radiotherapy was given for tumors and high-risk lymphatic drainage areas. 3. consolidation neochemotherapy will be started in 2-3w after concurrent chemoradiation: one cycle of XELOX regimen; From the beginning of induction chemo to 3w before surgery, PD-1 antibody SHR-1210 will be given q3W. Re-evaluation will be conducted in 1-3w after consolidation chemo, resectable patients will receive D2 resection. Adjuvant chemo: We advise starting 4 cycles of XELOX regimen in 4-6w after surgery.

Also known as: Newplan

Neoadjuvant therpy

Eligibility Criteria

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

You may qualify if:

• histologically documented gastric adenocarcinoma.
• primary lesion is in proximal stomach, including gastroesophageal junction, fundus and upper body.
• clinically diagnosed stage T3-4aN+M0 according to ultrasound endoscopy or enhanced CT/MRI scan.
• at least one evaluable lesion in abdominal CT/MRI according to RESIST 1.1 is required.
• surgeons participating in this study consider the lesion a resectable one.
• Karnofsky score≥ 80.
• Physical condition and adequate organ function to ensure the success of abdominal surgery.
• Adequate hematological function: Neutrophil count ≥ 1.5 × 109/L, Platelets ≥ 100 × 109/L and Hemoglobin ≥90g/L.
• Adequate liver function: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) \< 2.5 × ULN in the absence of liver metastases, or \< 5 × ULN in case of liver metastases. ALP ≤ 2.5 × upper limit of normal (ULN); ALB ≥30g/L.
• Adequate renal function: Serum creatinine ≤ 1.5 x ULN, and creatinine clearance ≥ 60 ml/min.
• Adequate coagulation function: INR/PT≤ 1.5 x ULN, aPTT≤ 1.5 x ULN.
• No serious concomitant disease that will threaten the survival of patients to less than 5 years.
• Male or female. Age ≥ 18 years and ≤75 years.
• Written (signed) informed consent.
• Good compliance with the study procedures, including lab and auxiliary examination and treatment.

You may not qualify if:

• patients with distant metastasis or unresectable primary lesion.
• patients with T1, T2 lesion according to CT/MRI or ultrasound endoscopy.
• history of chemo, radiation, immune therapy or radical resection for the stomach adenocarcinoma, except steroids.
• 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 or breast 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.
• patients with upper GI tract obstruction or functional abnormality or malabsorption syndrome, which can affect absorption of capecitabine.
• losing over 20% body weight in 2 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:

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Interventions

Neoadjuvant Therapy

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Study Officials

• Tianshu Liu, Doctor

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tianshu Liu, Doctor

CONTACT

+861368 1973 996; liu.tianshu@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Oncology Department

Study Record Dates

• First Submitted: August 13, 2018
• First Posted: August 15, 2018
• Study Start: August 20, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: August 26, 2020

Record last verified: 2020-08

Locations

CN (1)