Cervical Cancer, Precancerous Condition
Conditions
Keywords
cervical cancer, cervical intraepithelial neoplasia grade 3
Brief summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer or to treat early cancer. SGN-00101 may be effective in preventing the development of cervical cancer in patients who have cervical intraepithelial neoplasia. PURPOSE: This phase II trial is studying how well SGN-00101 immunotherapy works in preventing cervical cancer in patients with grade III cervical intraepithelial neoplasia.
Detailed description
OBJECTIVES: Primary * Determine the rate of regression at 4-7 months in patients with grade III cervical intraepithelial neoplasia (CIN III) treated with SGN-00101 immunotherapy. * Compare the rate of regression at 4-7 months with expected outcome in patients immunized with this vaccine. * Determine the toxic effects and recovery from possible toxic effects of this vaccine in these patients. Secondary * Determine induction of cell-mediated immune responses against human papillomavirus (HPV) E7 peptides before and after treatment in patients immunized with this vaccine * Correlate regression of disease with enhanced immunologic responses in patients immunized with this vaccine. * Correlate seropositivity of HPV-16 virus-like particles (VLP16) with vaccine-induced regression of CIN III in patients immunized with this vaccine. * Determine the efficacy of this vaccine in patients whose CIN III is associated with HPV-16 infection vs other HPV types. OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 treatment groups. All patients receive SGN-00101 subcutaneously once monthly on months 1-3 (for a total of 3 vaccinations) in the absence of disease progression or unacceptable toxicity. * Group 1: Four months after the first vaccination, patients undergo therapeutic and diagnostic loop electrosurgical excision procedure (LEEP) or core biopsy. * Group 2: Six months after the first vaccination, patients undergo therapeutic and diagnostic LEEP or core biopsy. Patients in group 1 are followed at 12 months and patients in group 2 are followed at 14 months after the first vaccination. PROJECTED ACCRUAL: A total of 66 patients (36 for group 1 and 30 for group 2) will be accrued for this study.
Interventions
BIOLOGICALHspE7
500 micrograms of SGN-00101 (HspE7, Nventa, San Diego, CA) is a novel therapeutic vaccine consisting of a fusion protein containing an M. bovis BCG heat shock protein (Hsp65) covalently linked to the entire sequence of HPV 16 E7.
Sponsors
National Cancer Institute (NCI)
Albert Einstein College of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
Parallel design
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed grade III cervical intraepithelial neoplasia (CIN III) with colposcopically visible cervical lesions * No positive endocervical curettage or inadequate colposcopy at the time of initial cervical biopsy PATIENT CHARACTERISTICS: Age * 18 and over Performance status * Not specified Life expectancy * Not specified Hematopoietic * WBC at least 3,500/mm\^3 * Lymphocyte count at least 500/mm\^3 * Platelet count at least 150,000/mm\^3 * Hemoglobin at least 10 g/dL * No significant hematologic disease that is uncontrolled with standard therapy Hepatic * Bilirubin no greater than 2 mg/dL * Liver enzymes no greater than 2.5 times normal * No significant hepatic disease that is uncontrolled with standard therapy Renal * Creatinine no greater than 2 mg/dL * No significant renal disease that is uncontrolled with standard therapy Cardiovascular * No significant cardiovascular disease that is uncontrolled with standard therapy Pulmonary * No significant respiratory disease that is uncontrolled with standard therapy * No history of asthma Immunologic * HIV negative * No clinical evidence of immunosuppression * No autoimmune disease * No history of allergic reactions attributed to compounds of similar chemical or biological activity as those used in this study * No history of a positive purified protein derivative (PPD) or Tine test Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Good health based upon the results of a medical history, physical examination, vital signs, and laboratory profile * No uncontrolled chronic disease * Chronic disease requiring medication is allowed provided the patient is not taking immunosuppressive drugs * No significant endocrine (e.g., thyroid or diabetes), neurologic, gastrointestinal, or dermatologic disease that is uncontrolled with standard therapy * No other underlying or unstable disease that would be exacerbated by the study treatment PRIOR CONCURRENT THERAPY: Biologic therapy * No prior BCG vaccination * No other concurrent vaccine therapy Chemotherapy * No concurrent chemotherapy Endocrine therapy * More than 30 days since prior oral or parenteral glucocorticoid steroid Radiotherapy * Not specified Surgery * Not specified Other * More than 30 days since prior participation in another investigational study * No concurrent cytotoxic therapy * No other concurrent investigational agents * No other concurrent investigational or commercial agents or therapies intended to treat CIN
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rate of regression | 4 months after completion of treatment |
| Toxicity | 4 months after completion of treatment |
Countries
United States
Outcome results
None listed