SGN-00101 Immunotherapy in Treating Patients With Grade III Cervical Intraepithelial Neoplasia

Study Overview
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Brief Summary
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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
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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.

Official Title
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SGN-00101 (HspE7) Immunotherapy Of CIN III

Conditions
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Cervical Cancer, Precancerous Condition

Intervention / Treatment
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* Biological: HspE7


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 month follow-up<br>3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 1 month; followed by LEEP or cone biopsy | Biological: HspE7<br>* 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.<br>* Other names: SGN-00101;|
| Active Comparator: 2 month follow-up<br>3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 2 months; followed by LEEP or cone biopsy | Biological: HspE7<br>* 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.<br>* Other names: SGN-00101;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of regression |  | 4 months after completion of treatment | 
| Toxicity |  | 4 months after completion of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cervical cancer, cervical intraepithelial neoplasia grade 3