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

Sponsor

Odense University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01295086

Collaborator

Aalborg University Hospital (Other), Aarhus University Hospital (Other), Rigshospitalet, Denmark (Other)

Enrollment

Locations

Arm

82.1

Actual Duration (Months)

6.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma	Drug: Docetaxel Drug: Oxaliplatin Drug: Capecitabine Drug: Trastuzumab	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Nov 1, 2014

Actual Study Completion Date :

Jan 1, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Her-TEX

Drug: Docetaxel

42, 51 or 60 mg/m² day 1 every 3. week

Other Names:

Taxotere

Drug: Oxaliplatin

100 mg/m² day 1 every 3. week

Other Names:

Eloxatin

Drug: Capecitabine

1250 mg/² continuously

Other Names:

Xeloda

Drug: Trastuzumab

Trastuzumab 8 mg/kg day 1, cycle 1. Following cycles 6 mg/kg every 3. week

Other Names:

Herceptin

Outcome Measures

Primary Outcome Measures

To determine maximum tolerable dose (MTD) for the combination regime TEX [2 years]
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.

Secondary Outcome Measures

Progression free survival [3 years]
Time from inclusion to disease progression or death of any cause.
Survival [4 years]
Time from inclusion to death of any cause.
Response rate [3 years]
According to RECIST version 1.1.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Aalborg University Hospital	Aalborg	Denmark	9100
2	Aarhus University Hospital	Aarhus	Denmark	8000
3	Rigshospitalet	Copenhagen	Denmark	2100
4	Odense University Hospital	Odense	Denmark	5000