Back to results

SOX Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of HER2-positive Locally Advanced Gastric Adenocarcinoma

Primary Purpose

HER2-positive, Locally Advanced Solid Tumor, Immunotherapy

Status

Not yet recruiting

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

sintilimab

Trastuzumab

S-1 plus oxaliplatin

About this trial

This is an interventional treatment trial for HER2-positive

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Sign the informed consent form.
Locally advanced adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II/III) confirmed by pathology or cytology.
The definition of a positive HER2 test result is as follows: IHC detects HER2 3+ or IHC detects HER2 2+ and FISH is positive.
Clinically, based on chest, abdomen and pelvic CT, gastroscopy, endoscopic ultrasonography, gastrointestinal contrast, ordinary ultrasound, or laparoscopy if possible, it is judged as T3-4a N+ or T4bN any gastric cancer or gastroesophageal junction cancer (refer to AJCC Article Version 8 in stages).
Patients have not received chemotherapy and/or immunotherapy and/or trastuzumab treatment and/or radiotherapy in the past.
Age 18-75 years old.
The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1, and there was no deterioration within 2 weeks before the first administration of the study drug.
Good organ function:

Blood routine: hemoglobin ≥90g/L, white blood cell ≥3.0×109/L, neutrophil ≥1.5×109/L, platelet ≥100×109/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥60ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL.

Exclusion Criteria:

The pathology is other types besides adenocarcinoma, such as squamous cell carcinoma, adenosquamous carcinoma, neuroendocrine carcinoma and so on.
Have received chemotherapy and/or radiotherapy in the past.
Have received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA-4 antibodies and other immunotherapy in the past.
Have received any anti-HER2 therapy in the past.
Intra-abdominal dissemination or distant metastasis (M1).
Clinically significant ascites.
Known to have allergic reactions to oxaliplatin and any ingredients or excipients of Tiggio.
Known to have allergic reactions to any ingredients or excipients of Sintilimab and Trastuzumab.
Inability to swallow, intestinal obstruction, or other factors that affect the administration and absorption of the drug.

Sites / Locations

Cancer Hospital & Institute, Chinese Academy of Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Group A

Group B

Arm Description

Group A: SOX regimen (oxaliplatin + Seggio) ) + sintilimab + trastuzumab; 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery

Group B: SOX regimen, 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery

Outcomes

Primary Outcome Measures

Major pathological response rate (MPR)

Proportion of subjects with residual tumor less than 10% or complete response

Secondary Outcome Measures

Pathological response rate (refer to Becker-TRG evaluation standard)

TRG level 1-3: 1a: No tumor remains at all 1b: Less than 10% of the tumor remains 2: 10%-50% tumor residual 3: More than 50% of the tumor remains or there is no change in the tumor

Objective response rate (ORR)

Proportion of subjects with initial RECIST 1.1 measurable disease who have complete response (CR) or partial response (PR) according to iRECIST

Disease-free survival (DFS)

Time from Cycle 1 Day 1 treatment administration to the first documented event of: disease progression, disease recurrence following surgery (preferably biopsy proven), or death - whichever occurs first.

Overall survival (OS)

Time from Cycle 1 Day 1 treatment administration to death due to any cause.

Incicende of Adverse Events (AEs)

Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE) assessed by CTCAE v5.0.

Biomarker assessment

To analyze the differences of gene and immune microenvironment biomarkers among patients with different curative effects, and further explore the relationship with the efficacy of clinical treatment. To analyze the correlation between peripheral blood indexes and the efficacy of clinical treatment.

Full Information

NCT ID

NCT05218148

First Posted

January 16, 2022

Last Updated

March 28, 2022

Sponsor

Aiping Zhou

1. Study Identification

Unique Protocol Identification Number

NCT05218148

Brief Title

SOX Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of HER2-positive Locally Advanced Gastric Adenocarcinoma

Official Title

Phase II Clinical Study of Oxaliplatin Plus S-1 (SOX) Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of Locally Advanced HER2-positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Not yet recruiting

Study Start Date

April 1, 2022 (Anticipated)

Primary Completion Date

October 1, 2024 (Anticipated)

Study Completion Date

December 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Aiping Zhou

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The SOX regimen has became the standard perioperative chemotherapy for locally advanced gastric cancer; The immune checkpoint inhibitors have become a standard treatment for advanced or metastatic gastric cancer；For HER2-positive locally advanced gastric cancer, some phase II studies have shown that chemotherapy combined with trastuzumab can further improve the pathological remission rate;This prospective phase II clinical trial was designed, using SOX combined with sintilimab and trastuzumab to treat HER2 positive locally advanced gastric or gastroesophageal junction adenocarcinoma patients.

Detailed Description

This phase II trial is a single-arm and single-center clinical study. Neoadjuvant chemotherapy is a standard treatment for locally advanced gastric cancer. The SOX regimen has became the standard perioperative chemotherapy regimen for locally advanced gastric cancer. For HER2-positive locally advanced gastric cancer, the neoadjuvant treatment is still based on chemotherapy alone. Some phase II studies have shown that chemotherapy combined with trastuzumab can further improve the pathological response. But it has not yet become a standard treatment strategy. In the field of gastric cancer, checkpoint inhibitors have become a standard treatment for advanced or metastatic gastric cancer. PD-1 monoclonal antibody (Sintilimab) + trastuzumab + chemotherapy (SOX regimen ) may be an ideal perioperative treatment for HER2-positive locally advanced gastric cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HER2-positive, Locally Advanced Solid Tumor, Immunotherapy, Sintilimab, S-1, Oxaliplatin, Gastric or Gastroesophageal Junction Adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

This is an open-label, randomized controlled, exploratory phase II study. Patients with HER2-positive locally advanced gastric or gastroesophageal junction adenocarcinoma who have not received any anti-tumor therapy were randomized in a 1:1 ratio to receive preoperatively: Group A: SOX regimen (oxaliplatin + Seggio) ) + sintilimab + trastuzumab; group B: SOX regimen, 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery

Masking

None (Open Label)

Allocation

Randomized

Enrollment

44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Group A

Arm Type

Experimental

Arm Description

Arm Title

Group B

Arm Type

Active Comparator

Arm Description

Group B: SOX regimen, 3 cycles of treatment, followed by D2 radical resection, and 5 cycles of adjuvant chemotherapy with the original regimen after surgery

Intervention Type

Drug

Intervention Name(s)

sintilimab

Intervention Description

Sintilimab 200mg was administered as a 30-60 min intravenous (IV) infusion every 3 weeks.3 cycles before surgery and 5 cycles after surgery.

Intervention Type

Drug

Intervention Name(s)

Trastuzumab

Intervention Description

Trastuzumab was 8mg/kg for the first time, and 6mg/kg for the follow-up. 3 cycles before surgery and 5 cycles after surgery.

Intervention Type

Drug

Intervention Name(s)

S-1 plus oxaliplatin

Intervention Description

Oxaliplatin 130 mg/m2 was administered IV every 3 weeks. S-1 was given orally twice daily for the first 2 weeks of each 3-week cycle. The S-1 dose was 40 mg for body surface area (BSA) < 1.25 m2, 50 mg for BSA 1.25 to <1.5 m2 and 60 mg for BSA ≥1.5 m2. Body surface area <1.25m2: Tegio 40mg bid day 1 ~ 14; Body surface area 1.25 ~ <1.5m2: Tegio 50mg bid day 1 ~ 14; Body surface area ≥1.5m2: Tegio 60mg bid day 1 ~ 14; 3 cycles before surgery and 3 cycles after surgery.

Primary Outcome Measure Information:

Title

Major pathological response rate (MPR)

Description

Proportion of subjects with residual tumor less than 10% or complete response

Time Frame

Up to 6 months

Secondary Outcome Measure Information:

Title

Pathological response rate (refer to Becker-TRG evaluation standard)

Description

TRG level 1-3: 1a: No tumor remains at all 1b: Less than 10% of the tumor remains 2: 10%-50% tumor residual 3: More than 50% of the tumor remains or there is no change in the tumor

Time Frame

Up to 3 years

Title

Objective response rate (ORR)

Description

Proportion of subjects with initial RECIST 1.1 measurable disease who have complete response (CR) or partial response (PR) according to iRECIST

Time Frame

Up to 3 years

Title

Disease-free survival (DFS)

Description

Time Frame

Up to 3 years

Title

Overall survival (OS)

Description

Time from Cycle 1 Day 1 treatment administration to death due to any cause.

Time Frame

Up to 3 years

Title

Incicende of Adverse Events (AEs)

Description

Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE) assessed by CTCAE v5.0.

Time Frame

Up to3 years

Title

Biomarker assessment

Description

Time Frame

Up to3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Sign the informed consent form. Locally advanced adenocarcinoma of the stomach or gastroesophageal junction (Siewert type II/III) confirmed by pathology or cytology. The definition of a positive HER2 test result is as follows: IHC detects HER2 3+ or IHC detects HER2 2+ and FISH is positive. Clinically, based on chest, abdomen and pelvic CT, gastroscopy, endoscopic ultrasonography, gastrointestinal contrast, ordinary ultrasound, or laparoscopy if possible, it is judged as T3-4a N+ or T4bN any gastric cancer or gastroesophageal junction cancer (refer to AJCC Article Version 8 in stages). Patients have not received chemotherapy and/or immunotherapy and/or trastuzumab treatment and/or radiotherapy in the past. Age 18-75 years old. The Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1, and there was no deterioration within 2 weeks before the first administration of the study drug. Good organ function: Blood routine: hemoglobin ≥90g/L, white blood cell ≥3.0×109/L, neutrophil ≥1.5×109/L, platelet ≥100×109/L; Renal function: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥60ml/min; Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL, AST≤2.5×UNL. Exclusion Criteria: The pathology is other types besides adenocarcinoma, such as squamous cell carcinoma, adenosquamous carcinoma, neuroendocrine carcinoma and so on. Have received chemotherapy and/or radiotherapy in the past. Have received any anti-PD-1, anti-PD-L1/L2 antibodies, anti-CTLA-4 antibodies and other immunotherapy in the past. Have received any anti-HER2 therapy in the past. Intra-abdominal dissemination or distant metastasis (M1). Clinically significant ascites. Known to have allergic reactions to oxaliplatin and any ingredients or excipients of Tiggio. Known to have allergic reactions to any ingredients or excipients of Sintilimab and Trastuzumab. Inability to swallow, intestinal obstruction, or other factors that affect the administration and absorption of the drug.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Aiping Zhou, doctor

Phone

86 13691161998

zhouap1825@126.com

Facility Information:

Facility Name

Cancer Hospital & Institute, Chinese Academy of Medical Sciences

City

Beijing

ZIP/Postal Code

100021

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

SOX Combined With Sintilimab and Trastuzumab Versus SOX Regimen in the Perioperative Treatment of HER2-positive Locally Advanced Gastric Adenocarcinoma

We'll reach out to this number within 24 hrs