Clinical trial NCT00083057: Gefitinib, Paclitaxel, and Radiation Therapy in Treating Patients With Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Head and Neck Cancer
Keywords: 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
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-05-17
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) as assessed by CTC v. 3.0
Secondary outcomes:
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
measure: Efficacy as assessed by imagining, histologically, and clinically at 3 months after completion of study treatment and annually for 5 years
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
city: Bethesda
country: United States
facility: NCI - Metabolism Branch;MET
state: Maryland
Study officials:
affiliation: National Institute on Deafness and Other Communication Disorders (NIDCD)
name: Carter Van Waes, MD, PhD
role: STUDY_CHAIR
affiliation: NCI - Metabolism Branch;MET
name: John C. Morris, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van Waes C, Allen CT, Citrin D, Gius D, Colevas AD, Harold NA, Rudy S, Nottingham L, Muir C, Chen Z, Singh AK, Dancey J, Morris JC. Molecular and clinical responses in a pilot study of gefitinib with paclitaxel and radiation in locally advanced head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):447-54. doi: 10.1016/j.ijrobp.2009.05.037. Epub 2009 Oct 30.
citation: Sharp H, Morris JC, Van Waes C, Gius D, Cooley-Zgela T, Singh AK. 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. 2008 Dec;31(6):557-60. doi: 10.1097/COC.0b013e318172d5de.
citation: 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.