OBJECTIVES:

• Compare the efficacy of SGN-00101 vs placebo in patients with grade II or III cervical intraepithelial neoplasia.
• Correlate clinical response, as defined by histologic demonstration of lesion regression, with potential surrogate markers of vaccine efficacy (e.g., spectroscopic changes in the epithelium, development of human papilloma virus (HPV)-specific mucosal and systemic T-cell responses, and levels of HPV-specific antibody in cervical secretions), in patients treated with this drug.

OUTLINE: This is a randomized, double-blind study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive SGN-00101 subcutaneously (SC) once a month for 3 consecutive months in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive placebo SC as in arm I. Patients are followed monthly for 3 months after the last injection and then undergo large loop excision of the transformation zone under colposcopy at the fourth month. Patients with disease progression undergo immediate large loop excision.

PROJECTED ACCRUAL: A maximum of 80 patients (40 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed grade II or III cervical intraepithelial neoplasia

  • Confirmed by colposcopy-directed punch biopsy

• Accessible, definable, and entirely visible cervical lesions persisting after biopsy

  • Satisfactory colposcopic exam within 3-6 weeks after diagnostic biopsy
• Positive for human papilloma virus 16
• CD4+ counts normal

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0

Life expectancy

• Not specified

Hematopoietic

• No coagulation disorder that requires medical intervention

Hepatic

• Hepatitis B core antigen negative
• Hepatitis C antibody negative

Renal

• Not specified

Cardiovascular

• No cardiovascular disorder that requires medical intervention

Pulmonary

• No respiratory disorder that requires medical intervention

Immunologic

• HIV negative
• Not immunologically compromised
• No prior severe allergic reactions (anaphylactic response) to drugs or any other allergen

• No immunological disorders including any of the following:

  • Lupus
  • Diabetes
  • Multiple sclerosis
  • Myasthenia gravis
• No active systemic infections that require medical intervention

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to undergo a loop electrosurgical excision procedure
• No medical or psychiatric illness that would preclude study treatment, ability to give informed consent, or study compliance
• No other prior malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No concurrent immunotherapy
• No other concurrent gene therapy
• No concurrent biologic therapy

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• More than 30 days since prior systemic steroid therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• More than 30 days since prior investigational drugs
• No other concurrent investigational drugs