Surgery and Vaccine Therapy in Treating Patients With Early Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from human papillomavirus may make the body build an immune response to and kill cervical cancer cells. Combining vaccine therapy with surgery may be a more effective treatment for cervical cancer. PURPOSE: This phase II trial is studying how well giving vaccine therapy together with surgery works in treating patients with early cervical cancer.

Detailed Description
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OBJECTIVES: Evaluate the systemic immunological response to the human papilloma virus vaccine (TA-HPV) expressing the proteins 16, 18, E6 and E7 examining the cytolytic T cell and the antibody responses in cervical cancer patients. Investigate further the safety and toxic effects of TA-HPV in these patients. Assess the proliferative capacity of T cells to the E6 and E7 proteins. Observe any influence of vaccination with TA-HPV on the disease free interval or patterns of recurrence in these patients. OUTLINE: This is an open-label, nonrandomized study. Patients receive 2 vaccinations of the human papilloma virus with proteins 16, 18, E6 and E7 at least 4 weeks apart, with the first vaccination at least 2 weeks before surgery and the second 8 weeks after the first one, unless unacceptable toxicity occurs. Patients who require radiotherapy following surgery receive their second vaccination 4-8 weeks after the first vaccination. Twenty-eight patients are entered initially; if at least 2 patients show an immunologic response, 16 additional patients are entered. Patients are followed every 3 months for 2 years, then every 6 months for 3 years, then annually. PROJECTED ACCRUAL: 44 patients will be entered over 1 year.

Official Title
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A Phase II Trial in Patients With Early Cervical Cancer to Study The Safety and The Immunological Effects of Vaccination With TA-HPV, A Live Recombinant Vaccinia Virus Expressing The Human Papilloma Virus 16 and 18 E6 and E7 Proteins

Conditions
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Cervical Cancer

Intervention / Treatment
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* Biological: human papillomavirus 16 E7 peptide
* Biological: synthetic human papillomavirus 16 E6 peptide
* Procedure: adjuvant therapy
* Procedure: surgical procedure
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven untreated stage Ib or IIa cervical carcinoma, squamous or adenocarcinoma suitable for surgical excision No CNS metastases Circulating CD4+ lymphocyte count at least 400 Proven absence of hepatitis B and C antibodies Previous exposure to vaccinia from smallpox vaccination, as well as no previous exposure, is allowed Reaction to 2 or more antigens on Pasteur Merieux CMI test required Ability to collaborate planned follow-up required PATIENT CHARACTERISTICS: Age: 19 and over Performance status: WHO/ECOG no greater than 2 Life expectancy: At least 3 months Hematopoietic: WBC greater than 3,000 (3,000 x 10 to the ninth/L) Platelet count greater than 120,000 (120 x 10 to the ninth/L) No bleeding disorder Hepatic: Bilirubin less than 1.5 times normal AST and ALT less than 1.5 times normal Prothrombin or partial thromboplastin time no greater than 2 times normal Renal: Creatinine less than 1.3 mg/dL (120 micromoles/L) Other: No ongoing infection No HIV antibody No serious medical or psychiatric illness No second malignancy within 5 years except for curatively treated basal cell skin cancer which required surgery, hormone therapy, immunotherapy or chemotherapy Not pregnant or nursing Adequate contraception required Patient or her household contacts must not have any of the following: Chronic steroid therapy Renal or other allograft Known immunodeficiency Eczema Children under 5 years old PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 19 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: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: human papillomavirus 16 E7 peptide|nan|
|Biological: synthetic human papillomavirus 16 E6 peptide|nan|
|Procedure: adjuvant therapy|nan|
|Procedure: surgical procedure|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunological response to HPV |  |  | 
| Toxicity and safety of TA-HPV |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proliferative capacity of T-cells to the E6 and E7 proteins |  |  | 
| Influence of vaccination with TA-HPV on the disease free interval or patterns of recurrence |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IB cervical cancer, stage IIA cervical cancer, cervical squamous cell carcinoma, cervical adenocarcinoma, cervical adenosquamous cell carcinoma