Gefitinib, Paclitaxel, and Radiation Therapy in Treating Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

March 14, 2012 updated by: National Institutes of Health Clinical Center (CC)

A Pilot Phase I Dose Escalation Study Of The EGFR Tyrosine Kinase Inhibitor Gefitinib (Iressa) Combined With Paclitaxel (Taxol) And External Beam Radiation Therapy In Patients With Advanced Squamous Cell Carcinoma Of The Head And Neck (SCCHN)

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving gefitinib and paclitaxel together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of gefitinib and paclitaxel when given together with radiation therapy in treating patients with advanced or recurrent squamous cell carcinoma (cancer) of the head and neck.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the dose-limiting toxicity, toxicity profile, and maximum tolerated dose (MTD) of gefitinib and paclitaxel administered with radiotherapy in patients with advanced or recurrent squamous cell carcinoma of the head and neck.

Secondary

  • Determine the efficacy of this regimen in patients treated at the MTD.

OUTLINE: This is a pilot, dose-escalation study of gefitinib and paclitaxel.

Patients receive oral gefitinib once daily beginning on day 1 and continuing until completion of radiotherapy. Patients receive paclitaxel IV over 1 hour on days 8, 15, 22, 29, 36, and 43 and undergo radiotherapy once daily on days 8-12, 15-19, 22-26, 29-33, 36-40, 43-47, 50-54, and 57-61. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gefitinib and paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A cohort of 6 additional patients receive treatment at the MTD.

Patients are followed monthly for 1 year, every 2 months for 1 year, and then every 3 months for 3 years.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 2 years.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
      • Bethesda, Maryland, United States, 20892-1547
        • NCI - Metabolism Branch;MET

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed squamous cell (epidermoid) carcinoma of the oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, or maxillary sinus

    • Stage III or IV disease

    • Distant metastases allowed provided both of the following are true:

      • Metastases are confined to the head and neck region
      • Metastases are encompassable in a radiotherapy field with curative intent
  • Locally recurrent disease after primary surgery allowed

  • Meets 1 of the following criteria:

    • Unresectable disease
    • Patient prefers chemoradiotherapy over surgery
  • Measurable disease
  • No brain metastases and/or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • WBC ≥ 3,000/mm^3
  • Hemoglobin > 10 g/dL
  • Platelet count > 100,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

  • Bilirubin < 2.0 times upper limit of normal (ULN)
  • AST/ALT ≤ 2.5 times ULN

Renal

  • Creatinine < 1.5 times ULN OR
  • Creatinine clearance ≥ 60 mL/min

Cardiovascular

  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Pulmonary

  • No clinically active interstitial lung disease

    • Chronic, stable, asymptomatic radiographic changes allowed

Other

  • No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs or Cremophor^® EL
  • No AIDS or primary immunodeficiencies

  • No other malignancy within the past 5 years except curatively treated squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

    • Probability of recurrence of the prior malignancy < 5%
  • No other concurrent uncontrolled illness
  • No ongoing or active serious infection
  • No psychiatric illness or situation that would preclude study compliance or giving informed consent
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy for cancer
  • No other concurrent chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior therapeutic radiotherapy to the head and neck region
  • No prior radiotherapy for cancer

Surgery

  • See Disease Characteristics
  • At least 4 weeks since prior major surgery and recovered

Other

  • No prior gefitinib or other epidermal growth factor receptor inhibitors
  • More than 4 weeks since prior non-approved or investigational agents

  • No concurrent administration of any of the following:

    • Phenytoin
    • Carbamazepine
    • Barbiturates
    • Rifampin
    • Hypericum perforatum (St. John's wort)
    • Oxcarbazepine
    • Rifapentine
    • Amifostine
    • Modafinil
    • Other CYP3A4 enzyme inducers
    • Other anticancer agents or investigational drugs
    • Combination antiretroviral therapy for HIV-positive patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) as assessed by CTC v. 3.0

Secondary Outcome Measures

Outcome Measure
Molecular targets analysis of epidermal growth factor receptor (EGFR) downstream signaling pathway as assessed by tissue biopsies and serum cytokines at baseline, days 8 and 29, and 12 weeks after completion of study treatment
Efficacy as assessed by imagining, histologically, and clinically at 3 months after completion of study treatment and annually for 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institutes of Health Clinical Center (CC)

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Carter Van Waes, MD, PhD, National Institute on Deafness and Other Communication Disorders (NIDCD)
  • Principal Investigator: John C. Morris, MD, NCI - Metabolism Branch;MET

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2004

Primary Completion (Actual)

October 1, 2010

Study Completion (Actual)

November 1, 2010

Study Registration Dates

First Submitted

May 14, 2004

First Submitted That Met QC Criteria

May 14, 2004

First Posted (Estimate)

May 17, 2004

Study Record Updates

Last Update Posted (Estimate)

March 15, 2012

Last Update Submitted That Met QC Criteria

March 14, 2012

Last Verified

March 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 040141
  • 04-C-0141
  • CDR0000362055

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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