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

NCT ID: NCT00083057

Last Updated: 2012-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-05-31
• Study Completion Date: 2010-11-30

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.

Conditions

Head and Neck Cancer

Study Design

• Primary Study Purpose: TREATMENT

Interventions

gefitinib

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

National Institutes of Health Clinical Center (CC)

NIH

Sponsor Role: lead

Principal Investigators

Carter Van Waes, MD, PhD

Role: STUDY_CHAIR

National Institute on Deafness and Other Communication Disorders (NIDCD)

John C. Morris, MD

Role: PRINCIPAL_INVESTIGATOR

NCI - Metabolism Branch;MET

Locations

Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support

Bethesda, Maryland, United States

NCI - Metabolism Branch;MET

Bethesda, Maryland, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 19879702 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19060587 (View on PubMed)

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.

Reference Type: RESULT

Other Identifiers

04-C-0141

Identifier Type: -

Identifier Source: secondary_id

CDR0000362055

Identifier Type: -

Identifier Source: secondary_id

040141

Identifier Type: -

Identifier Source: org_study_id

NCT00080249

Identifier Type: -

Identifier Source: nct_alias