Gene Therapy in Treating Patients With Advanced Head and Neck Cancer

University of Pittsburgh

Status and phase: Completed; Phase 1

Conditions: Head and Neck Cancer

Treatments: Biological: EGFR antisense DNA; Drug: DC-cholesterol liposome; Biological: growth factor antagonist therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00009841

NCI-G00-1904

PCI-IRB-980771

CDR0000068414 (Registry Identifier)

PCI-98025

Details and patient eligibility

About

RATIONALE: Gene therapy may kill cancer cells by inhibiting a gene that promotes the development and growth of cancer.

PURPOSE: Phase I trial to study the effectiveness of gene therapy in treating patients who have advanced head and neck cancer.

Full description

OBJECTIVES: I. Determine the safety and biological activity of EGFR antisense DNA and DC-chol liposomes in patients with advanced squamous cell carcinoma of the head and neck. II. Determine the toxicity and maximum tolerated dose of this regimen in these patients. III. Determine the antitumor response in patients treated with this regimen. IV. Determine the effect of this regimen on EGFR expression levels, STAT protein expression/activation levels, and apoptosis rates in biopsied tumor cells of these patients.

OUTLINE: This is a dose-escalation study. Patients receive EGFR antisense DNA and DC-chol liposomes intratumorally weekly for 4 weeks. Courses repeat every 4 weeks for up to 6 months in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of EGFR antisense DNA and DC-chol liposomes until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 6 patients experience dose-limiting toxicity. Patients are followed at 1 month.

PROJECTED ACCRUAL: A total of 20-36 patients will be accrued for this study.

Enrollment: 13 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS: Histologically confirmed advanced squamous cell carcinoma of the head and neck Primary or recurrent disease Not amenable to standard therapy (surgery, chemotherapy, or radiotherapy) Second primary lesions allowed Brain metastases allowed after definitive radiotherapy

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT no greater than 4 times normal Renal: Creatinine no greater than 2 mg/dL Calcium no greater than 10.5 mg/dL Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception (double-barrier method and oral contraception) prior to, during, and for at least 2 weeks after study

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 4 weeks since prior biologic therapy Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery: See Disease Characteristics