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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)


Phase 1
18 Years
N/A
Not Enrolling
Both
Head and Neck Cancer

Thank you

Trial Information

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)


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.

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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

Yes

Principal Investigator

Carter Van Waes, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

National Institute on Deafness and Other Communication Disorders (NIDCD)

Authority:

United States: Food and Drug Administration

Study ID:

040141

NCT ID:

NCT00083057

Start Date:

May 2004

Completion Date:

November 2010

Related Keywords:

  • Head and Neck Cancer
  • 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
  • Carcinoma
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasms

Name

Location

Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182
NCI - Metabolism Branch;METBethesda, Maryland  20892-1547