Clinical trial NCT00004097: Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Advanced and/or Recurrent Head and Neck Cancer
Official title: A Phase I Study of Concomitant Chemoradiotherapy With Gemcitabine, Paclitaxel, and 5-FU for Patients With Advanced and/or Recurrent Cancer of the Head and Neck
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Head and Neck Cancer
Keywords: stage III nasopharyngeal cancer
stage IV nasopharyngeal cancer
recurrent nasopharyngeal cancer
untreated metastatic squamous neck cancer with occult primary
recurrent metastatic squamous neck cancer with occult primary
stage III lip and oral cavity cancer
stage IV lip and oral cavity cancer
recurrent lip and oral cavity cancer
stage III hypopharyngeal cancer
stage IV hypopharyngeal cancer
recurrent hypopharyngeal cancer
stage III laryngeal cancer
stage IV laryngeal cancer
recurrent laryngeal cancer
stage III paranasal sinus and nasal cavity cancer
stage IV paranasal sinus and nasal cavity cancer
recurrent paranasal sinus and nasal cavity cancer
stage III oropharyngeal cancer
stage IV oropharyngeal cancer
recurrent oropharyngeal cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-03-31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use 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. Combining chemotherapy with radiation therapy may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus radiation therapy in treating patients who have advanced and/or recurrent head and neck cancer.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of gemcitabine when administered with paclitaxel and fluorouracil with concurrent hyperfractionated radiotherapy in patients with advanced and/or recurrent head and neck cancer. II. Determine the MTD and DLT of gemcitabine as a single agent with radiotherapy in these patients. III. Determine the efficacy of concurrent chemoradiotherapy in terms of time to progression, pattern of failure, and overall survival in patients with measurable disease. IV. Determine gemcitabine and fluorouracil pharmacokinetics in these patients.

OUTLINE: This is a dose escalation study of gemcitabine, conducted in two phases. Phase A: Patients receive fluorouracil IV continuously on days 1-5, paclitaxel IV over 1 hour on day 2, and radiotherapy administered twice daily on days 1-5. This regimen is repeated every 2 weeks for 2 courses, then gemcitabine IV over 30 minutes is added on day 2 after paclitaxel. This regimen is administered every 2 weeks for 3 courses. Patients with responsive disease may continue chemotherapy (without radiotherapy) for 2 courses beyond maximum response. Cohorts of 3-6 patients receive escalating doses of gemcitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 3 of 6 patients experience dose-limiting toxicity. Phase B: After the MTD of gemcitabine is determined in phase A, further dose escalation of gemcitabine may be performed with concurrent radiotherapy (without fluorouracil or paclitaxel). The MTD is determined as in phase A. Patients are followed monthly for 1 year and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study within approximately 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically proven head and neck cancer requiring regional radiotherapy Locoregional, recurrent disease after primary therapy with surgery, radiation, or both OR Stage IV, no prior therapy, and not amenable to conventional therapy with curative intent Metastatic disease allowed if predominant site and associated symptoms require local treatment in the head and neck region

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: WBC greater than 3,000/mm3 Absolute neutrophil count greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 mg/dL Transaminases no greater than 2.5 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Other: Not pregnant or nursing Fertile patients must use effective contraception No significant infection No other severe medical illness

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Recovered from any prior chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics Recovered from any prior radiotherapy Surgery: See Disease Characteristics Recovered from any prior surgery

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center, Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Athanassios Argiris, MD
role: STUDY_CHAIR
References: