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

NCT ID: NCT00075569

Last Updated: 2018-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-03-31
• Study Completion Date: 2005-08-31

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.

Conditions

Cervical Cancer; Precancerous Condition

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

HspE7

Intervention Type: BIOLOGICAL

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.

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

Group Type: ACTIVE_COMPARATOR

HspE7

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

SGN-00101

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Albert Einstein College of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carolyn D. Runowicz, MD

Role: STUDY_CHAIR

UConn Health

Mark H. Einstein, MD, MS

Role:

Albert Einstein College of Medicine

Locations

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Countries

United States

References

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. doi: 10.1016/j.ygyno.2007.04.038. Epub 2007 Jun 22.

Reference Type: RESULT

PMID: 17586030 (View on PubMed)

Other Identifiers

AECOM-0309225

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-5850

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

03-10-251

Identifier Type: -

Identifier Source: org_study_id