- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04819971
Study of Perioperative Chemotherapy Combined With Tislelizumab and Trastuzumab in the Treatment of GC/EGC
April 23, 2023 updated by: Feng Wang, The First Affiliated Hospital of Zhengzhou University
Efficacy and Safety of Perioperative Chemotherapy Combined With Tislelizumab and Trastuzumab in Patients With HER2-positive Resectable Gastric or Gastr-oesophageal Junction Carcinoma (GC/EGJ) -- a Prospective, Single-arm, Phase II Study
Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA).
The addition of tislelizumab and trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and the investigators aimed to explore its role in the perioperative setting.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed Description
This study will evaluate the pathologic complete response rate of a perioperative chemotherapy combined with tislelizumab and Trastuzumab in patients with resectable gastric cancer.
Prior to surgery to resect the tumor, tislelizumab (intravenously, 200 mg on day 1 of every cycle) and trastuzumab (intravenously, 8 mg/kg loading dose, then 6 mg/kg on days 1 of every cycle) will be administered for four cycles and the perioperative chemotherapy contains docetaxel (intravenously, 50 mg/m2 on day 1 of every cycle) and S1 (orally, 400mg/m2 BID on day 1~14 of every cycle) and Oxaliplatin(intravenously, 100 mg /m2 on day 1 of every cycle) will be administered for three cycles prior to surgery.If complete resection, R0 or microscopic residual tumor R1 is achieved, patients will continue with three cycles of SOX and tislelizumab and trastuzumab and then for completion of 12 months treatment with tislelizumab and trastuzumab alone.
Study Type
Interventional
Enrollment (Anticipated)
67
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: feng wang, doctor
- Phone Number: +8613938244776
- Email: zzuwangfeng@zzu.edu.cn
Study Locations
-
-
Henan
-
Zhengzhou, Henan, China
- Recruiting
- The First Affiliated hospital of Zhengzhou University
-
Contact:
- feng wang
- Phone Number: +8613938244776
- Email: zzuwangfeng@zzu.edu.cn
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Key Inclusion Criteria:
- provide archive tumor tissue samples or accept fresh tumor tissue biopsy(Sample requirements are: formalin-fixed and paraffin-embedded wax blocks of tumor tissue or at least 20 unstained tumor specimen slides).
assessed by the surgery can be removed, histology/confirmed HER2 positive cytology and the integration of a stomach esophagus carcinoma.
- CT2-4CN any C M0 or T any CN +M0, AJCC/UICC TNM staging of gastric cancer (8th edition).
- The HER2 receptor protein status was assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) using the following methods.Tumors with an IHC 3+ score are considered HER2-positive.Patients with immunohistochemical 2+ tumors were given FISH tests to determine FISH positive samples.
- Abdominal computed tomography (CT), abdominal, pelvic, and/or echo-endoscopy were performed 2 weeks before surgery to assess resectability.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or 2.
- have no received no any anti-tumor treatment, including surgery, chemotherapy, targeted therapy, immune therapy.
- Adequate organ function (No blood transfusion or hematopoietic stimulating factor therapy was received within 14 days. Absolute neutrophil count (ANC) ≥1.5×109/L Platelet count ≥75×109/L Hemoglobin ≥80 g/L. Serum total bilirubin ≤1.5×ULN. total bilirubin must be <3×ULN) Prothrombin time/international normalized ratio (PT/INR) ≤1.5×ULN and activated partial thromboplastin time (aPTT) ≤1.5×ULN.Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤3×ULN. For subjects with liver metastases, AST and ALT must be ≤5×ULN for subjects with liver metastases. Creatinine clearance rate (Ccr) ≥50ml/min(according to the Cockcroft-Gault formula). Urine protein qualitative≤1+ ;Or urinary protein qualitative ≥2+, 24 hours urinary protein < 1g)
Key Exclusion Criteria:
- A history of any other malignancy in the past 5 years (except carcinoma in situ or basal cell carcinoma of the skin or squamous cell carcinoma of the skin)
- Received other unmarketed investigational drug or therapy within 4 weeks prior to initial investigational drug use.
- A major organ surgery (excluding needle biopsy) or significant trauma occurred within 4 weeks prior to initial investigational drug use.
- Requires systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration to treat a current condition.
Exceptions include: topical, ocular, intraarticular, intranasal, and inhaled glucocorticoids;Short-term use of glucocorticoids for preventive treatment (e.g. to prevent contrast allergy)
- Use of immunoregulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., within 14 days prior to initial use of the study drug.
- Has been administered a live vaccine within 4 weeks prior to Cycle1 Day 1.
- Previous recipient of allogeneic hematopoietic stem cell transplantation or organ transplantation.
- Previous adverse reactions to other medications have not recovered to CTCAE 5.0 level ≤1 (Other toxicities, such as hair loss, were not considered to pose a safety risk).
- Symptomatic peripheral neuropathy was evaluated as > 2 with CTCAE 5.0.
- Has central nervous system metastases or meningeal metastases.
- Inability to swallow medications orally, or other gastrointestinal diseases (such as total intestinal obstruction, etc.) that may affect the absorption of oral medications.
- Patients who had an active infection within 1 week prior to the first use of the study drug and who currently require systemic anti-infective therapy.
- has a history of alcohol or drug abuse or dependence.
- Known history of Human Immunodeficiency Virus (HIV).
- Untreated chronic hepatitis B viral (HBV) infection or chronic HBV carrier with HBV DNA ≥200 IU/mL (or 1000 copies/mL),prophylaxis antiviral therapy other than interferon is allowed ,or active hepatitis C virus (HCV) should be excluded.
- Current patients with interstitial lung disease.
- Has a history of severe cardiovascular and cerebrovascular disease, including but not limited to: has serious heart rhythm or abnormal conduction;Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to D1 ;New York heart association (NYHA), cardiac function class II or higher and left ventricular ejection fraction (LVEF) < 50%; clinical uncontrol of high blood pressure.
- Patients with active, or previous and recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) were excluded from patients with clinically stable autoimmune thyroid disease.
- Grade 3 or higher arteriovenous thromboembolism events or bleeding events occurred within 6 months prior to the first use of the study drug;Or present with grade ≥2 bleeding or factors determined by the investigator to have a higher blood risk (such as active gastrointestinal ulcer or esophageal varicose veins or tumor invasion of major blood vessels).
- Gastrointestinal perforation, abdominal fistula or intraperitoneal abscess occurred within 6 months prior to the first use of the study drug;Or a risk factor for cavity perforation/fistula formation (e.g., tumor infiltration of the outer wall of the cavity wall) currently identified by the investigator.
- Patients who allergies to the study drugs.
- People with mental disorders or poor compliance.
- Women who are pregnant or lactating.
- The investigator considers the subject to have a history of other serious systemic disease or for other reasons unsuitable for participation in this clinical study.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: TTC
|
Trastuzumab(intravenously, 8 mg/kg loading dose, then 6 mg/kg on days 1 of every cycle for 4 preoperative and 12 postoperative cycles)
docetaxel (intravenously, 50 mg/m2 on day 1 of every cycle for 3 preoperative cycles)
S1 (orally, 400mg/m2 BID on day 1~14 of every cycle for 3 preoperative and 3 postoperative cycles )
Oxaliplatin(intravenously, 100 mg /m2 on day 1 of every cycle for 3 preoperative cycles ;130mg /m2 on day 1 of every cycle for 3 postoperative cycles.
tislelizumab (intravenously, 200 mg on day 1 of every cycle for 4 preoperative and 12 postoperative cycles)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Pathological Complete Response (pCR)
Time Frame: 2 years
|
pCR was defined as an absence of any invasive cancer cell of the primary tumor after the time of major neoadjuvant chemotherapy, with or without surgery.
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Complete Tumor Resection (R0)
Time Frame: 75 days
|
R0 resection was defined as having performed a complete resection of the tumor with adequate tumor-free margins and regional lymph node extirpation.
|
75 days
|
Percentage of Participants With Disease-free Survival (DFS)
Time Frame: 2 years
|
DFS was the time elapsed from the time of surgery (for complete resection [R0] participants) until the date on which progression or death from any cause was documented (whichever occured first).
Progression was defined as target lesions greater than (>) 20 percent (%) increase in the sum of the longest diameter (SLD) taking as reference the smallest SLD recorded since the treatment started (nadir) and minimum 5 millimeter (mm) increase over the nadir.
When the sum becomes very small, increases within the measurement error (2-3 mm) can lead to a 20% increase.
Participants who did not present progression and who had not died were censored on the last date on which it was known that there was no progression (last response assessment).
|
2 years
|
Overall Survival (OS)
Time Frame: 2 years
|
OS was defined as the time from randomization to death due to any cause.
Participants without documented death at the time of the final analysis were censored at the date of the last follow-up.
OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group.
|
2 years
|
Percentage of All Participants That Discontinued Study Treatment Due to AE
Time Frame: 2 years
|
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure.
Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE.
The percentage of participants that discontinued study treatment due to an AE was reported for all participants by treatment group.
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2021
Primary Completion (Anticipated)
December 31, 2025
Study Completion (Anticipated)
December 31, 2025
Study Registration Dates
First Submitted
March 21, 2021
First Submitted That Met QC Criteria
March 26, 2021
First Posted (Actual)
March 29, 2021
Study Record Updates
Last Update Posted (Actual)
April 25, 2023
Last Update Submitted That Met QC Criteria
April 23, 2023
Last Verified
April 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Stomach Diseases
- Stomach Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Immunological
- Docetaxel
- Trastuzumab
- Oxaliplatin
Other Study ID Numbers
- TIS-HER2GC-PERIOPERATIVE-IIT
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Stomach Cancer
-
Jeeyun LeeRecruitingStomach Cancer, AdenocarcinomaKorea, Republic of
-
Chinese University of Hong KongUnknown
-
Chinese University of Hong KongUnknown
-
Ohio State University Comprehensive Cancer CenterPharmacia and UpjohnCompletedStomach Cancer | Esophageal Cancer | Cancer of Stomach | Esophagus CancerUnited States
-
BayerCompletedPrevention of Oesophagus Cancer and Stomach CancerUnited Kingdom
-
Chinese University of Hong KongRecruiting
-
Dana-Farber Cancer InstituteMassachusetts General Hospital; Genentech, Inc.; SCRI Development Innovations... and other collaboratorsCompletedStomach Cancer | Gastric Cancer | Esophageal CancerUnited States
-
Xijing Hospital of Digestive DiseasesCompletedStomach Cancer | Esophageal Cancer | Esophageal Dysplasia | Stomach DysplasiaChina
-
MacroGenicsMerck Sharp & Dohme LLCCompletedStomach Cancer | Gastric Cancer | Esophageal CancerKorea, Republic of, United States, Taiwan, Singapore, Canada
-
Dana-Farber Cancer InstituteMassachusetts General Hospital; Genentech, Inc.; Brigham and Women's HospitalCompletedStomach Cancer | Esophageal CancerUnited States
Clinical Trials on Trastuzumab
-
National Cancer Institute (NCI)NRG OncologyActive, not recruitingBreast Ductal Carcinoma In SituUnited States, Canada, Puerto Rico, Korea, Republic of
-
Tanvex BioPharma USA, Inc.CompletedBreast Cancer | Breast Neoplasms | HER2-positive Breast Cancer | Stage II Breast Cancer | Stage IIIA Breast Cancer | Early-stage Breast CancerBelarus, Chile, Georgia, Hungary, India, Mexico, Peru, Philippines, Russian Federation, Ukraine
-
Spanish Breast Cancer Research GroupCompleted
-
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen UniversityRecruitingHER2-positive Breast Cancer | Early-stage Breast Cancer | Adjuvant Treatment After Trastuzumab | RCB Classification 1-2 | NeratiniChina
-
Fudan UniversityHoffmann-La RocheUnknown
-
Orano Med LLCCompletedStomach Neoplasms | Breast Neoplasms | Pancreatic Neoplasms | Ovarian Neoplasms | Peritoneal NeoplasmsUnited States
-
National Cancer Institute (NCI)Active, not recruitingMale Breast Carcinoma | Stage IIA Breast Cancer AJCC v6 and v7 | Stage IIB Breast Cancer AJCC v6 and v7 | Stage IIIA Breast Cancer AJCC v7 | Stage IIIB Breast Cancer AJCC v7 | Stage IIIC Breast Cancer AJCC v7United States, Puerto Rico
-
Fudan UniversityCompleted
-
Samsung Bioepis Co., Ltd.TerminatedBreast NeoplasmsUkraine, Romania, Russian Federation, France, Bulgaria, Czechia, Poland
-
University Medical Center GroningenCompleted