Anti-HER2 Therapy in Patients of HER2 Positive Metastatic Carcinoma of Digestive System

  • End date
    Sep 22, 2021
  • participants needed
  • sponsor
    Shen Lin
Updated on 22 January 2021
platelet count
systemic therapy
measurable disease
squamous cell carcinoma
neutrophil count
liver metastasis
digestive system tumor


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.


Human epidermal growth factor receptor 2, (HER2) is overexpressed /amplified in multiple carcinomas, for example, gastric cancer(GC), gastroesophageal junction adenocarcinoma(GEJA),and breast cancer.And HER2 is closely related to tumor proliferation &metastases.About 90% Chinese esophagus cancer are squamous cell origin. The reported HER2 overexpression ranged from 5-30%, Beijing cancer hospital reported an 11% positive rate. The variety of HER2 positive rate may because of the absence of standard HER2 testing criteria. The current treatment for metastatic Esophageal squamous Cell Carcinoma (ESCC) is not satisfactory. Fluorouracil and platinum are considered as first line standard of care (SOC) with a 20-30% RR and 7-9 months overall survival (OS). In second line setting, there is no SOC in china. And the efficacy is not satisfactory. Esophageal adenocarcinoma has a higher HER2 positive rate of 14%, but no data reported of using trastuzumab in these patients in China. Biliary tract cancer (BTC), including intrahepatic/extrahepatic cholangiocarcinoma and Gallbladder cancer (GBC) is very aggressive, total 5y survival is less than 5% for unresectable patients. GBC is account for approximately 2/3 of BTC, and it's estimated the incidence in china is 52800 and the mortality is 40700 in 2015. Most patients are diagnosed in advanced stage and lose the opportunity of surgery. However, there is no SOC for unresectable BTC, gemcitabine plus platinum provided a 30% RR and 10 month OS. In second line treatment, no differences were seen between various experimental agents. The reported HER2 positive rate range from 5.1% to 57% in biliary duct cancer and 4.7% to 64% in GBC. Researchers reported her2 amplification is related to tumor stage and lymph nodes metastasis in 221 BTC patients. Another study reported a 16.6% positive rate and worse prognosis with a sample size of 230 GBC patients. Meanwhile, HER2 pathway mutation rate reached 37%. All imply that BTC may be the potential anti HER therapy population. Besides, other digestive system tumor has low HER2 positive rate (Small intestinal cancer 0.9-3%; hepatocellular carcinoma 2.4%; Pancreatic cancer 3%; etc.). However, the patient pool is large and has no SOC in second Line. Whether these HER2 + patients can gain benefit form anti- her treatment is worth investigating. In 2016 American Society of Clinical Oncology (ASCO), a study reported that using trastuzumab and pertuzumab combination, 35% metastatic colorectal cancer (CRC) and 50% BTC patients who heavily pretreated had objective response. However, china doesn't have studies for these patients. .

The concurrent basket trial will explore the efficacy and safety of trastuzumab with chemotherapy in Chinese patients of pretreated, HER2 positive, relapse or metastatic carcinoma of digestive system.

Condition Colorectal Cancer, Rectal disorder, Biliary neoplasm, Esophageal Cancer, ERBB2 gene, Squamous cell carcinoma, HER2, Colon Cancer Screening, Rectal Disorders, Colon cancer; rectal cancer, Esophageal Squamous Cell Carcinoma, Squamous Cell Carcinoma of Esophagus, Targeted Therapy, Urothelial Tract Cancer, Biliary Tract Cancer, colorectal neoplasm, erbb2, human epidermal growth factor receptor 2, her2/neu, colorectal cancers, her-2, cancer, colorectal, colorectal tumor, tumors, colorectal, biliary cancer
Treatment chemotherapy in combination with trastuzumab for arm1, chemotherapy in combination with trastuzumab for arm2, chemotherapy in combination with trastuzumab for arm3, chemotherapy in combination with trastuzumab for arm4
Clinical Study IdentifierNCT03185988
SponsorShen Lin
Last Modified on22 January 2021


Yes No Not Sure

Inclusion Criteria

Is your age between 18 yrs and 75 yrs?
Gender: Male or Female
Do you have any of these conditions: Biliary neoplasm or HER2 or Colorectal Cancer or Targeted Therapy or ERBB2 gene or Esophageal Squamous Cell Carcinoma?
Do you have any of these conditions: ERBB2 gene or Colorectal Cancer or Esophageal Squamous Cell Carcinoma or Squamous cell carcinoma or her2/neu or Colon Cancer Screening or colorectal t...?
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
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 hybridizationSISH or chromogenic in situ hybridizationCISH 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
ULN OR creatinine clearance 40 mL/ min
If able to reproduce, patients must be willing to use highly effective methods of contraception during treatment and for 7 months after the end of treatment

Exclusion Criteria

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
Known HIV or hepatitis B virus(HBV), hepatitis C virus(HCV) infection
Any > grade 1 unresolved toxicity due to previous treatment (CTC-AE), except for alopecia, anemia and hypothyroidism)
Not suitable for the study evaluated by investigators
Known dihydropyrimidine dehydrogenase (DPD) deficiency
History of exposure to the following cumulative doses of anthracyclines
Doxorubicin > 500 mg/m2 OR Epirubicin > 720 mg/m2
If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin
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