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

Sponsored by:	Swiss Group for Clinical Cancer Research
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00445861

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 Drug: cisplatin Drug: docetaxel Procedure: conventional surgery Procedure: neoadjuvant therapy Radiation: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Radiation Therapy Surgery

Drug Information available for: Cisplatin Docetaxel Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Limiting toxicity of radiotherapy in combination with weekly chemoimmunotherapy [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

30-day postoperative survival after completion of therapy [ Designated as safety issue: No ]
Adverse events according to CTCAE version 3.0 [ Designated as safety issue: Yes ]
Pathological remission [ Designated as safety issue: No ]
R0 resection rate [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Time to local failure after R0 resection [ Designated as safety issue: No ]
Time to systemic failure after R0 resection [ Designated as safety issue: No ]

Estimated Enrollment:	27
Study Start Date:	January 2007
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

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

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

Kantonsspital - St. Gallen

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000530672, SWS-SAKK-75/06, EU-20702
Study First Received:	March 7, 2007
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00445861 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus
stage II esophageal cancer
stage III esophageal cancer

Study placed in the following topic categories:

Digestive System Neoplasms
Gastrointestinal Diseases
Esophageal Neoplasms
Cetuximab
Esophageal Cancer
Squamous Cell Carcinoma
Carcinoma
Docetaxel
Digestive System Diseases

Radiation-Sensitizing Agents
Cisplatin
Esophageal Disorder
Head and Neck Neoplasms
Epidermoid Carcinoma
Gastrointestinal Neoplasms
Esophageal Diseases
Carcinoma, Squamous Cell
Adenocarcinoma

Additional relevant MeSH terms:

Digestive System Neoplasms
Gastrointestinal Diseases
Antineoplastic Agents
Esophageal Neoplasms
Physiological Effects of Drugs
Cetuximab
Pharmacologic Actions
Docetaxel
Neoplasms

Digestive System Diseases
Neoplasms by Site
Radiation-Sensitizing Agents
Cisplatin
Therapeutic Uses
Head and Neck Neoplasms
Gastrointestinal Neoplasms
Esophageal Diseases

ClinicalTrials.gov processed this record on May 06, 2009