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.
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.
Brief Title
SGN-00101 Immunotherapy in Treating 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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Cervical Cancer
Precancerous Condition
Eligibility 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
* 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
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
* 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
Female
Gender Based
false
Keywords
cervical cancer
cervical intraepithelial neoplasia grade 3
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
120 Years
Minimum Age
18 Years
NCT Id
NCT00075569
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
03-10-251
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
SGN-00101 (HspE7) Immunotherapy Of CIN III
Primary Outcomes
Outcome Measure
Rate of regression
Outcome Time Frame
4 months after completion of treatment
Outcome Measure
Toxicity
Outcome Time Frame
4 months after completion of treatment
Secondary Ids
Secondary Id
AECOM-0309225
Secondary Id
NCI-5850
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
120
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Mark Einstein
Investigator Email
meinstei@montefiore.org
Investigator Phone