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Trastuzumab

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HER2 positive GI tumor beyond CRC, ESCC, BTC,GC\&GEJA

HER2 positive Esophageal squamous cell carcinoma

HER2 positive and RAS/BRAF wild type colorectal cancer

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)

chemotherapy in combination with trastuzumab for arm1

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.

chemotherapy in combination with trastuzumab for arm2

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.

chemotherapy in combination with trastuzumab for arm3

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)

chemotherapy in combination with trastuzumab for arm4

Xicheng Wang, Dr.

xicheng wang, Doctor

Lin Shen, Master

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.

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

The percentage of patients, whose tumor volume in first time shrink to pre-defined criteria, including CR and PR

The percentage of patients who achieve complete remission(CR) or partial remission (PR) or stable disease(SD) determined by the RECIST v1.1 criteria.

The percentage of patients who achieve either a CR or PR as determined by the RECIST v1.1 criteria based on investigator's assessment that is confirmed by a repeat assessment performed no less than 4 weeks after the criteria for response are first met.

Defined as the initiation of treatment to the day of first documentation of PD or date of death, whichever occurs first.

Is the time from the initiation of treatment to the date of death from any cause.

Defined as the initiation of treatment to the day of first documentation of response.

Only patients who achieve an objective response will be included in the analysis.

Defined as the time from the date of the first documented objective response to the date of first documented PD or death, whichever occurs first. Only patients who achieve an objective response will be included in the analysis.

Defined as the initiation of treatment to the day of first documentation of PD.

Spots Global Cancer Trial Database for chemotherapy in combination with trastuzumab for arm2