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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00083057
First received: May 14, 2004
Last updated: March 14, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Head and Neck Cancer
Drug: gefitinib
Drug: paclitaxel
Radiation: radiation therapy
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) as assessed by CTC v. 3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Designated as safety issue: No ]
  • Efficacy as assessed by imagining, histologically, and clinically at 3 months after completion of study treatment and annually for 5 years [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2004
Study Completion Date: November 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00083057

Locations
United States, Maryland
NCI - Metabolism Branch;MET
Bethesda, Maryland, United States, 20892-1547
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
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
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00083057     History of Changes
Obsolete Identifiers: NCT00080249
Other Study ID Numbers: 040141, 04-C-0141, CDR0000362055
Study First Received: May 14, 2004
Last Updated: March 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institutes of Health Clinical Center (CC):
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Paclitaxel
Gefitinib
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 19, 2014