Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Gefitinib, Paclitaxel, and Radiation Therapy in Treating Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck (Closed to Accrual as of 8/24/2009)

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI	NCI-04-C-0141 5926, NCT00083057

Objectives

Primary

1. 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

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

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC ≥ 3,000/mm³
• Hemoglobin > 10 g/dL
• Platelet count > 100,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³

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

Expected Enrollment

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

Outcomes

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

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

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.

Sharp H, Morris JC, Van Waes C, et al.: High incidence of oral dysesthesias on a trial of gefitinib, Paclitaxel, and concurrent external beam radiation for locally advanced head and neck cancers. Am J Clin Oncol 31 (6): 557-60, 2008.[PUBMED Abstract]

Sharp HJ, Morris JC, Van Waes C, et al.: A high incidence of oral dysesthesias unrelated to mucositis in a pilot trial of gefitinib, paclitaxel and concurrent external beam radiation in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). [Abstract] Int J Radiat Oncol Biol Phys 66 (3 Suppl 1): A-1101, S188-9, 2006.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Carter Van Waes, MD, PhD, Protocol chair		Ph: 301-402-4216
John Morris, MD, Principal investigator		Ph: 301-402-2912 Email: jmorris@mail.nih.gov

Related Information

Web site for additional information

Registry Information
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)
Trial Start Date		2004-05-28
Registered in ClinicalTrials.gov		NCT00083057
Date Submitted to PDQ		2004-03-17
Information Last Verified		2007-02-05

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