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

Gastric Adenocarcinoma Clinical Trial

Official title: A Phase II Study of Neoadjuvant Chemoradiation Plus PD-1 Antibody(SHR-1210) in the Locally Advanced Proximal Stomach Adenocarcinoma (Neo-PLANET)

Status Recruiting

Clinical Trial Summary

1. Target population: patients with resectable locally advanced proximal (including gastroesophageal junction, fundus and upper body) stomach adenocarcinoma (cT3-4aN+M0).

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.

Secondary objectives:

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

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

3. progression free survival (PFS)/ overall survival (OS) of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210)

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

3.Trial design: This is a monocenter, single arm, phase II study to evaluate the efficacy and safety of neoadjuvant chemoradiation plus PD-1 antibody (SHR-1210) in patients with locally advanced proximal stomach adenocarcinoma.

4.Treatment plan:

Patients will be given the perioperative treatment as below once recruited:

1. induction chemotherapy (3w): one cycle of XELOX regimen (capecitabine 1000 mg/m2 bid*14d + oxaliplatin 130mg/m2, d1, Q21d);

2. 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.

3. 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).

Re-evaluation will be conducted in 1-3w after consolidation chemo, resectable patients will receive D2 resection.

Adjuvant chemo: We advice starting 4 cycles of XELOX regimen (capecitabine 1000 mg/m2 bid*14d + oxaliplatin 130mg/m2, d1, Q21d) in 4-6w after surgery.

5.Number of subjects: 36 patients. Number of centers: 1 sites ( Fudan University Affiliated Zhongshan Hospital, which has high volume of gastric operations in China, more than 500 per year).

Clinical Trial Description

Backgrounds:

SHR-1210 is a PD-1 antibody developed by Jiangsu Heng Rui Medicine Co. Nowadays, fifteen clinical trials of this drug have been conducted in patients with different types of advanced malignant tumor, including one combined with radiotherapy and three combined with chemotherapy. Until now, SHR-1210 has exhibited favorable safety in recruited patients. Incidence rate of SAE is only 1%.

Several big scale clinical research like POET, RTOG 9904 and TOPGEAR have proofed the efficacy and safety of neoadjuvant chemoradiation in treating locally advanced GEJ cancer or gastric cancer.

Study design:

This clinical trial will be conducted under Simon's optimal two-stage design. The first stage needs 15 participants, if ≥1 participants acquire remission, then the study will move on to the second stage and enroll the rest 21 participants. The total sample size will be 36 patients.

We will shut down the study in advance, if situations below happens: 1) 1 treatment related death, >3 disease progression or >2 hyper-progressive disease happen during the first stage; 2) 2 treatment related death, >6 disease progression or >4 hyper-progressive disease happen during the whole study.

Patients with abnormal autoimmune status, unfavorable body function, factors impeding drug taking, absorption and metabolism will be excluded. Study participants with disease progression or severe/ intolerant toxicity during treatment will withdraw the study.

Hyper-progressive disease is defined as 1) progression 2) more than doubled growth rate 3) tumor volume increase >50% in 2 months after initialing the treatment. ;

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Adenocarcinoma

• NCT number: NCT03631615
• Study type: Interventional
• Source: Shanghai Zhongshan Hospital
• Contact: Tianshu Liu, Doctor
• Phone: +861368 1973 996
• Email: liu.tianshu@zs-hospital.sh.cn
• Status: Recruiting
• Phase: Phase 2
• Start date: August 20, 2018
• Completion date: December 2020