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Cetuximab, Docetaxel, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed by Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT00445861
First received: March 7, 2007
Last updated: June 8, 2012
Last verified: June 2012
  Purpose

RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving cetuximab, docetaxel, and cisplatin together with radiation therapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase I/II trial is studying the side effects of cetuximab, docetaxel, cisplatin, and radiation therapy and to see how well they work in treating patients with locally advanced esophageal cancer that can be removed by surgery.


Condition Intervention Phase
Esophageal Cancer
Biological: cetuximab + docetaxel + cisplatin
Biological: Treatment level 1
Biological: Treatment level 2
Procedure: conventional surgery
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cetuximab in Combination With Radiation Therapy and Chemotherapy Prior to Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma. A Multicenter Phase IB-II Trial

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin [ Time Frame: Until treatment ends ] [ Designated as safety issue: Yes ]
    Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin


Secondary Outcome Measures:
  • Determine the feasibility and efficacy of the study's regimen [ Time Frame: Until trial ends ] [ Designated as safety issue: No ]
    Determine the feasibility and efficacy of this regimen in these patients.

  • Determine the duration of response and patterns of failure [ Time Frame: Until trial ends ] [ Designated as safety issue: Yes ]
    Determine the duration of response and patterns of failure in patients treated with this regimen


Enrollment: 27
Study Start Date: January 2007
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: cetuximab + docetaxel + cisplatin
    Chemoimmunotherapy: Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-3 and docetaxel IV over 1 hour and cisplatin IV over 1 hour once in week 1. Treatment repeats every 3 weeks for 2 courses.
    Biological: Treatment level 1
    Treatment level 1: Patients receive cetuximab IV over 1 hour once weekly, cisplatin IV over 1 hour once weekly, and undergo radiotherapy once daily, 5 days a week, in weeks 7-11.
    Biological: Treatment level 2
    Patients receive cetuximab, cisplatin, and radiotherapy as in treatment level 1. Patients also receive docetaxel IV over 1-2 hours once weekly in weeks 7-11.
    Procedure: conventional surgery
    Between 4-8 weeks after completion of neoadjuvant chemoimmunotherapy and radiotherapy, patients undergo surgery.
Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety of neoadjuvant radiotherapy in combination with cetuximab, docetaxel, and cisplatin in patients with resectable locally advanced esophageal cancer.

Secondary

  • Determine the feasibility and efficacy of this regimen in these patients.
  • Determine the duration of response and patterns of failure in patients treated with this regimen.

OUTLINE: This is a multicenter study.

  • Chemoimmunotherapy: Patients receive cetuximab IV over 1-2 hours once weekly in weeks 1-3 and docetaxel IV over 1 hour and cisplatin IV over 1 hour once in week 1. Treatment repeats every 3 weeks for 2 courses.
  • Chemoimmunotherapy and radiotherapy: Patients are sequentially assigned to 1 of 2 treatment levels.

    • Treatment level 1: Patients receive cetuximab IV over 1 hour once weekly, cisplatin IV over 1 hour once weekly, and undergo radiotherapy once daily, 5 days a week, in weeks 7-11.
    • Treatment level 2: Patients receive cetuximab, cisplatin, and radiotherapy as in treatment level 1. Patients also receive docetaxel IV over 1-2 hours once weekly in weeks 7-11.

Cohorts of 7-20 patients are treated at treatment level 1 or 2 sequentially, as long as no more than 2 of 7 patients experience dose-limiting toxicity (DLT), until the safe treatment level for future study is determined. The safe treatment level is defined as the level at which no more than 2 of 7 and no more than 6 of 20 patients experience DLT. At least 20 patients are treated at the safe treatment level.

  • Surgery: Between 4-8 weeks after completion of neoadjuvant chemoimmunotherapy and radiotherapy, patients undergo surgery.

After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed squamous cell carcinoma or adenocarcinoma of the thoracic esophagus

    • Carcinoma of the gastroesophageal junction (i.e., Siewert staging system type I disease) allowed
  • Locally advanced disease

    • Obstructive tumors are considered locally advanced disease
    • Meets 1 of the following staging criteria:

      • T3, N0 disease
      • T1-3, N1 disease
      • T4, N0-1 disease
  • Resectable disease

    • No T4 (unequivocal organ involvement) disease that cannot be resected with curative intent
  • No airway infiltration in case of tumors of the upper third of the thoracic esophagus
  • No cervical esophageal carcinoma
  • No distant metastasis, including stage M1a (celiac node involvement) by fine-needle aspiration or biopsy

PATIENT CHARACTERISTICS:

  • WHO performance status 0-1
  • Creatinine clearance > 60 mL/min
  • Bilirubin normal
  • Alkaline phosphatase ≤ 2.5 times upper limit of normal (ULN)
  • AST ≤ 1.5 times ULN
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study treatment
  • No other malignancy within the past 5 years except nonmelanomatous skin cancer or adequately treated in situ cervical cancer
  • No severe or uncontrolled cardiovascular disease including, but not limited to, any of the following:

    • New York Heart Association class III or IV congestive heart failure
    • Unstable angina pectoris
    • Myocardial infarction within the past 3 months
    • Significant arrhythmias
  • No psychiatric disorder that would preclude study compliance
  • No active uncontrolled infection
  • No serious underlying medical condition that, in the opinion of the investigator, would interfere with study participation (e.g., uncontrolled diabetes mellitus or active autoimmune disease)
  • No peripheral neuropathy > grade 1
  • No contraindications to corticosteroids
  • No known hypersensitivity to any component of the study drugs

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy
  • No prior radiotherapy to the chest
  • No participation in another clinical trial within the past 30 days
  • No other concurrent experimental drugs or anticancer therapy
  • No concurrent drugs contraindicated for use with the study drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445861

Locations
Switzerland
Kantonsspital - St. Gallen
St. Gallen, Switzerland, CH-9007
Klinik Stephanshorn
St. Gallen, Switzerland, Ch-9016
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Thomas Ruhstaller, MD Cantonal Hospital of St. Gallen
  More Information

Publications:
Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT00445861     History of Changes
Other Study ID Numbers: SAKK 75/06, EU-20702
Study First Received: March 7, 2007
Last Updated: June 8, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site
Cetuximab
Cisplatin
Docetaxel
Antimitotic Agents
Antineoplastic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on November 25, 2014