Cidofovir in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer Who Are Receiving Chemotherapy and Radiation Therapy

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs such as cidofovir may make tumor cells more sensitive to radiation therapy. Giving cidofovir together with radiation therapy and chemotherapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of cidofovir in treating patients with stage IB, stage II, stage III, or stage IVA cervical cancer who are receiving chemotherapy together with radiation therapy.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of cidofovir when given as a radiosensitizer in patients with stage IB-IVA cervical cancer undergoing concurrent chemoradiotherapy. Secondary Evaluate the influence of treatment on the expression of mRNA codons in HPV oncoproteins E6 and E7. Determine the rate of local control. OUTLINE: This is a dose-escalation study of cidofovir. Patients receive cidofovir IV weekly for 2 weeks prior to beginning radiotherapy and then once biweekly during radiotherapy. Patients undergo external pelvic radiotherapy for 5 weeks. Beginning ≤ 2 weeks later, patients undergo utero-vaginal brachytherapy. Some patients may also undergo a second course of external radiotherapy to the parametrium and/or lymph nodes ≤ 3 days after brachytherapy. Patients also receive concurrent carboplatin IV once weekly during external radiotherapy and brachytherapy. Biological expression of HPV oncoproteins E6 and E7 is analyzed during treatment.

Official Title
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Modulating the Expression of Oncoproteins of Papillomavirus (HPV) to Increase Radiosensitivity: a Phase I Study of Antiviral Agent Cidofovir and Chemoradiotherapy Therapy in Cervical Cancers

Conditions
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Cervical Cancer, Precancerous Condition

Intervention / Treatment
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* Drug: carboplatin
* Drug: cidofovir
* Genetic: protein expression analysis
* Other: laboratory biomarker analysis
* Radiation: brachytherapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of squamous cell carcinoma or adenocarcinoma of the cervix Stage IB2 (> 4 cm), II, III, or IVA disease No lumbo-aortic metastasis Initial tumor must be HPV-positive PATIENT CHARACTERISTICS: WHO performance status 0-1 Life expectancy > 3 months ANC > 2,000/mm^3 Platelet count > 100,000/mm^3 Hemoglobin ≥ 9 g/dL Transaminases < 1.5 times upper limit of normal (ULN) Alkaline phosphatase < 1.5 times ULN Bilirubin < 1.5 times ULN Creatinine < 1.5 times ULN Creatinine clearance ≥ 55 mL/min Proteinuria < 2 g/L Not pregnant Negative pregnancy test No renal disease No concurrent active infection No prior or concurrent psychiatric illness No history of cancer except for basal cell carcinoma No other active infection or serious illness that would prevent the patient from receiving study treatment No known psychological, familial, social, or geographic reason that would preclude clinical monitoring PRIOR CONCURRENT THERAPY: No prior radiotherapy or chemotherapy More than 30 days since prior experimental drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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 |
| --- |
|Drug: carboplatin|nan|
|Drug: cidofovir|nan|
|Genetic: protein expression analysis|nan|
|Other: laboratory biomarker analysis|nan|
|Radiation: brachytherapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of cidofovir |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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human papilloma virus infection, cervical squamous cell carcinoma, cervical adenocarcinoma, stage IB cervical cancer, stage II cervical cancer, stage III cervical cancer, stage IVA cervical cancer