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

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)

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.

Study Overview

• Status: Completed
• Conditions: Adenocarcinoma
• Intervention / Treatment: Drug: Docetaxel; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Trastuzumab

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9100
    • Aalborg University Hospital
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Odense University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with histologically proven ECV-adenocarcinoma, non-resectable or metastatic disease
2. HER2-positive tumor tissue (IHC 3 + or FISH positive)
3. LVEF > 50 % (MUGA scan or echocardiography)
4. Age ≥ 18 years
5. No prior chemotherapy
6. WHO performance status 0-1
7. Life expectancy of at least 3 months
8. Neutrophils ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L
9. 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
10. Creatinine clearance ≥ 50 ml/min. Calculated with the Cockroft-Gault formula
11. No neuropathy
12. Planned treatment start within 8 days after inclusion

Exclusion Criteria:

1. Patients who cannot complete treatment or evaluation
2. 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
3. Known hypersensitivity towards any of the study drugs
4. Other malignant disease within the last 5 days, except for non-melanoma skin cancer
5. Other serious disease (e.g. cardiac disease, AMI within 1 year or infection)
6. Pregnant women or nursing women
7. Physical or mental conditions which may prevent absorption of oral treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Aarhus University Hospital; Rigshospitalet, Denmark; Aalborg University Hospital
• Investigators: Study Chair: Per Pfeiffer, Professor, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: February 11, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 14, 2011

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 29, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Xeloda (Capecitabine); Taxotere (Docetaxel); Dose finding; Her2; Adenocarcinoma of the gastro-esophageal; Eloxatin (Oxaliplatin); Herceptin (Trastuzumab)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab; Capecitabine; Oxaliplatin
• Other Study ID Numbers: Her-TEX