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

Albert Einstein College of Medicine

Status and phase: Completed; Phase 2

Conditions: Precancerous Condition; Cervical Cancer

Treatments: Biological: HspE7

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00075569

AECOM-0309225 (Other Identifier)

NCI-5850 (Other Grant/Funding Number)

03-10-251

Details and patient eligibility

About

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.

Full 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.

Enrollment: 64 patients

Sex: Female

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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64 participants in 2 patient groups

1 month follow-up

Active Comparator group

Description:

3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 1 month; followed by LEEP or cone biopsy

Treatment:

Biological: HspE7

2 month follow-up

Active Comparator group

Description:

3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 2 months; followed by LEEP or cone biopsy

Treatment:

Biological: HspE7