Anti-HER2 Therapy in Patients of HER2 Positive Metastatic Carcinoma of Digestive System
Multicenter, Phase II Study of Chemotherapy in Combination With Trastuzumab in Patients of Pretreated, HER2 Positive, Relapse or Metastatic Carcinoma of Digestive System
1 other identifier
interventional
100
1 country
1
Brief Summary
To seek the efficacy signals of trastuzumab in combination with chemotherapy in pretreated patients of HER2 positive, relapse or metastatic carcinoma of digestive system as response rate (RR) determined by the Investigator using RECIST 1.1, and provide evidence for phase III clinical trial.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2017
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2017
CompletedFirst Posted
Study publicly available on registry
June 14, 2017
CompletedStudy Start
First participant enrolled
July 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
September 1, 2021
CompletedJuly 19, 2019
July 1, 2019
4 years
May 16, 2017
July 17, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Response Rate(RR) for each cohort in intent to treat (ITT) population
The percentage of patients, whose tumor volume in first time shrink to pre-defined criteria, including CR and PR
baseline up to death or disease progression,which ever occurs first(up to approximately 8.5 years)
Secondary Outcomes (9)
Disease control rate
baseline up to death or disease progression,which ever occurs first(up to approximately 8.5 years)
best overall response
10-30 weeks
Progression free survival
baseline up to death or disease progression,which ever occurs first(up to approximately 8.5 years)
Overall survival
baseline up to death or disease progression,which ever occurs first(up to approximately 8.5 years)
time to response
6-30 weeks
- +4 more secondary outcomes
Study Arms (4)
GI tumor beyond CRC, ESCC, BTC,GC&GEJA
EXPERIMENTALHER2 positive GI tumor beyond CRC, ESCC, BTC,GC\&GEJA
Esophageal squamous cell carcinoma
EXPERIMENTALHER2 positive Esophageal squamous cell carcinoma
Biliary tract cancer
EXPERIMENTALHER2 positive Biliary tract cancer
Colorectal cancer
EXPERIMENTALHER2 positive and RAS/BRAF wild type colorectal cancer
Interventions
Arm1: GI tumor beyond CRC, ESCC, BTC and GC\&GEJA Trastuzumab (Herceptin ®): 6 mg/kg every 3 weeks (8 mg/kg as loading dose at 1st administration), iv, d1.The first infusion is to be given over 90 minutes, and subsequent infusions are to be given over 30 minutes if the first infusion is well tolerated.Combined chemotherapy (by investigator's choice)
Arm2: esophageal squamous cell carcinoma (ESCC) Trastuzumab (Herceptin ®): the same as above Combined with Irinotecan: 120 mg/m2 IV, day 1 and day 8, every 3 weeks.
Arm 3: biliary tract cancer (BTC) Trastuzumab (Herceptin®): the same as above Combined chemotherapy (by investigator's choice) The combined chemotherapy of cohort 1 and 3 is Irinotecan: 120 mg/m2 IV, day 1and day 8, every 3 weeks. OR 5-Fu: 720 mg/m2/day, continuous IV. Infusion over 5 days, every 3 weeks. OR Capecitabine(Xeloda®):1000 mg/m2 bid, d1-d14, every 3 weeks. The chemotherapy regimen is chosen at the Investigator's discretion and can be determined on an individual patient basis. Special cases should be discussed with the principal investigator.
Trastuzumab (Herceptin ®): same as above Combined with Irinotecan: 120 mg/m2 iv, day 1and day 8, every 3 weeks. OR Capecitabine(Xeloda®)1000 mg/m2 bid, d1-d14, every 3 weeks. OR Irinotecan: 120 mg/m2 iv, day 1and day 8 and Capecitabine(Xeloda®)1000 mg/m2 bid, d1-d14, every 3 weeks (by investigator's choice)
Eligibility Criteria
You may qualify if:
- Signed informed consent.
- Male and female patients aged from 18 to 75 years
- Histologically confirmed Colorectal cancer,Esophagus squamous cell carcinoma, biliary tract cancer, and digestive system tumor beyond CRC and GC\&GEJA with the following specifications:
- genetic testing conformed KRAS/NRAS/BRAF all wild type for colorectal cancer
- Detection of a carcinoma with HER2 3+ (IHC) or HER2 2+ (IHC) with amplification proven by fluorescence in situ hybridization(FISH), silver in situ hybridization（SISH） or chromogenic in situ hybridization（CISH） using gastric cancer criteria by an accredited local pathologist.
- Relapse or metastatic diseases, at least one measurable lesion according to RECIST 1.1, anticipated survival ≥ 12 weeks.
- ECOG Performance status 0-1.
- Patients who failed at least first line systemic therapy.
- Adequate organ function as determined by the following laboratory results:
- Absolute neutrophil count ≥1500 cells/mm3,
- Platelet count ≥ 90,000 cells/mm3,
- Hemoglobin ≥9.0 g/dL
- Total bilirubin ≤ 1.5 upper limit of normal (ULN).
- serum glutamate oxaloacetate transaminase(SGOT,AST), serum glutamate pyruvate transaminase(SGPT,ALT) \< 2.5 ULN without liver metastases; \< 5 ULN with liver metastases.
- serum creatinine \< 1.5
- +2 more criteria
You may not qualify if:
- Known hypersensitivity against treatment regimen.
- Baseline left ventricular ejection fraction(LVEF) \< 50% (measured by echocardiography or MUGA).
- Previous anti-her treatment.
- Immune therapy, biological therapy or any participation in clinical trial in previous two weeks.
- Surgery and not recovered in previous three weeks
- Clinical evidence of brain metastases, or uncontrolled epilepsy.
- Serious uncontrolled systemic intercurrent illness, e.g. infections or poorly controlled diabetes.
- Other malignancy within the last 5 years, except for carcinoma in situ of the cervix, or basal cell carcinoma.
- Clinically significant active coronary heart disease, cardiomyopathy or congestive heart failure, New York Heart Association(NYHA) III-IV; poorly controlled hypertension (systolic BP \> 180 mmHg or diastolic BP \> 100 mmHg); clinically significant valvular heart disease; unstable angina pectoris, myocardial infarction or high risk uncontrollable arrhythmias.
- Long term or high dose corticosteroids administration ( inhalation or short term oral administration for antiemesis and orexigenic is allowed)
- Patients of legally incapacity or of medical and ethical reasons not fit for study.
- Pregnant or lactating, or intending to become pregnant during the study.
- Jaundice, ascites, and / or alkaline phosphatase ≥3 × ULN; and / or ≥3 grade (CTC-AE) of persistent proteinuria, urinary protein / creatinine ratio\> 3.5g / 24 hours or renal failure need blood or peritoneal dialysis.
- Presence of \> grade 2(CTC-AE) persistent infection; unhealed wounds, ulcer or fracture, or patients with a history of organ transplant.
- Evidence of coagulation disorders. Like presence ≥grade 3 (CTC-AE) bleeding events.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Shen Linlead
Study Sites (1)
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142, China
Related Publications (1)
Xu T, Wang X, Xin Y, Wang Z, Gong J, Zhang X, Li Y, Ji C, Sun Y, Zhao F, Huang D, Bai Y, Li J, Shen L. Trastuzumab Combined with Irinotecan in Patients with HER2-Positive Metastatic Colorectal Cancer: A Phase II Single-Arm Study and Exploratory Biomarker Analysis. Cancer Res Treat. 2023 Apr;55(2):626-635. doi: 10.4143/crt.2022.1058. Epub 2022 Dec 23.
PMID: 36550683DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Lin Shen, Master
Director
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Prof.
Study Record Dates
First Submitted
May 16, 2017
First Posted
June 14, 2017
Study Start
July 1, 2017
Primary Completion
July 1, 2021
Study Completion
September 1, 2021
Last Updated
July 19, 2019
Record last verified: 2019-07
Data Sharing
- IPD Sharing
- Will not share