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

• Status: Unknown status
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shen Lin
• Treatments: Capecitabine; Irinotecan; Trastuzumab

Criteria

Inclusion Criteria:

• 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

• 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.