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

Overview

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 Title of Study: “SGN-00101 (HspE7) Immunotherapy Of CIN III”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 2005

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

  • Biological: HspE7
    • 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.

Arms, Groups and Cohorts

  • Active Comparator: 1 month follow-up
    • 3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 1 month; followed by LEEP or cone biopsy
  • Active Comparator: 2 month follow-up
    • 3 monthly subcutaneous vaccinations with 500 microg of HspE7 followed by monthly colposcopic follow-up for 2 months; followed by LEEP or cone biopsy

Clinical Trial Outcome Measures

Primary Measures

  • Rate of regression
    • Time Frame: 4 months after completion of treatment
  • Toxicity
    • Time Frame: 4 months after completion of treatment

Participating in This Clinical Trial

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

Gender Eligibility: Female

Minimum Age: 18 Years

Maximum Age: 120 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Albert Einstein College of Medicine
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Carolyn D. Runowicz, MD, Study Chair, UConn Health
    • Mark H. Einstein, MD, MS, , Albert Einstein College of Medicine

Citations Reporting on Results

Einstein MH, Kadish AS, Burk RD, Kim MY, Wadler S, Streicher H, Goldberg GL, Runowicz CD. Heat shock fusion protein-based immunotherapy for treatment of cervical intraepithelial neoplasia III. Gynecol Oncol. 2007 Sep;106(3):453-60. Epub 2007 Jun 22.

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