Taxotere®, Eloxatin® and Xeloda® (TEX) in Combination With Herceptin® as Treatment for HER2 Positive Non-resectable Cancer

Study Overview
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Brief Summary
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The primary aim of this dose-finding study is to determine the maximum tolerated dose of taxotere, eloxatin and capecitabine (TEX) in combination with herceptin given every third week as first-line treatment in patients with HER2-positive advanced gastro-esophageal cancer. Secondary end points are to evaluate progression-free survival and overall survival.

Detailed Description
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Primary aim: To define the maximum tolerated dose of the combination of taxotere, eloxatin and capecitabine (TEX) in combination with herceptin given every third week as first- line treatment in patients with HER2-positive advanced gastro-esophageal cancer. Secondary aims: Estimating response-rate, progression free survival and overall survival Methods: This dose-finding study is planned to include 15 patients with HER2 positive gastro-esophageal cancer, adenocarcinoma. Patients will be included in cohorts of three at progressively higher dose levels. Chemotherapy will be repeated day 1 every third week to a maximum of eight cycles. Treatment with trastuzumab will continue until disease progression. Dose-limiting toxicity (DLT) will be evaluated after the first cycle. In case of DLT among one of the three patients during the first course of treatment additional three patients will be added at the respective dose level. Dose escalation is continued if 0/3 or 1/6 patients experience DLT. Patients will be evaluated with a ct- scan at baseline and after every three cycles to exclude progression and evaluate response. Response is assessed by investigators according to RECIST version 1.1. Blood counts regarding tumour biology will be collected at baseline before 2nd, 4th and 7th cycle and 4 weeks after ended treatment. After completion of treatment patients will be followed every third month until progression or death.

Official Title
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Dose Determination of Taxotere®, Eloxatin® and Xeloda® (TEX)in Combination With Herceptin® as First-line Treatment for Patients With HER2 Positive Non-resectable Oesophagus, Cardia or Gastric Cancer (ECV)

Conditions
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Adenocarcinoma

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Oxaliplatin
* Drug: Capecitabine
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically proven ECV-adenocarcinoma, non-resectable or metastatic disease HER2-positive tumor tissue (IHC 3 + or FISH positive) LVEF > 50 % (MUGA scan or echocardiography) Age ≥ 18 years No prior chemotherapy WHO performance status 0-1 Life expectancy of at least 3 months Neutrophils ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L Bilirubin ≤ 1.5 x UNL (Upper Normal Limit) and ASAT and/or ALAT ≤ 3 x UNL. In case of liver metastases no UNL for ASAT and ALAT Creatinine clearance ≥ 50 ml/min. Calculated with the Cockroft-Gault formula No neuropathy Planned treatment start within 8 days after inclusion Exclusion Criteria: Patients who cannot complete treatment or evaluation Any condition or treatment which after the opinion of the investigator may expose the patients to a risc or influence the purpose of the study Known hypersensitivity towards any of the study drugs Other malignant disease within the last 5 days, except for non-melanoma skin cancer Other serious disease (e.g. cardiac disease, AMI within 1 year or infection) Pregnant women or nursing women Physical or mental conditions which may prevent absorption of oral treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Her-TEX<br> | Drug: Docetaxel<br>* 42, 51 or 60 mg/m² day 1 every 3. week<br>* Other names: Taxotere;Drug: Oxaliplatin<br>* 100 mg/m² day 1 every 3. week<br>* Other names: Eloxatin;Drug: Capecitabine<br>* 1250 mg/² continuously<br>* Other names: Xeloda;Drug: Trastuzumab<br>* Trastuzumab 8 mg/kg day 1, cycle 1. Following cycles 6 mg/kg every 3. week<br>* Other names: Herceptin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine maximum tolerable dose (MTD) for the combination regime TEX | The investigators have planned to examine 3 dose levels including 3 patients at each level with escalating doses of docetaxel from 42 mg/m² to 60 mg/m² and fixed doses of oxaliplatin (100 mg/m²), capecitabine 625 mg/m² x 2 and trastuzumab 6 mg/kg. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival | Time from inclusion to disease progression or death of any cause. | 3 years | 
| Survival | Time from inclusion to death of any cause. | 4 years | 
| Response rate | According to RECIST version 1.1. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adenocarcinoma of the gastro-esophageal, Her2, Dose finding, Taxotere (Docetaxel), Eloxatin (Oxaliplatin), Xeloda (Capecitabine), Herceptin (Trastuzumab)