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

S

Swiss Group for Clinical Cancer Research

Status and phase

Completed
Phase 2
Phase 1

Conditions

Esophageal Cancer

Treatments

Biological: Treatment level 2
Biological: Treatment level 1
Biological: cetuximab + docetaxel + cisplatin
Procedure: conventional surgery

Study type

Interventional

Funder types

Other

Identifiers

NCT00445861
SAKK 75/06
EU-20702

Details and patient eligibility

About

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.

Full 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.

Enrollment

27 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

Trial contacts and locations

2

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Data sourced from clinicaltrials.gov

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