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

Condition(s) targeted: Cervical Cancer; Precancerous Condition

Intervention: carboplatin (Drug); cidofovir (Drug); protein expression analysis (Genetic); laboratory biomarker analysis (Other); brachytherapy (Radiation); radiation therapy (Radiation)

Phase: Phase 1

Status: Recruiting

Sponsored by: Institut Gustave Roussy

Official(s) and/or principal investigator(s):
Eric Deutsch, MD, Affiliation: Institut Gustave Roussy

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.

Official title: 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

Study design: Primary Purpose: Treatment

Primary outcome: Maximum tolerated dose of cidofovir

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 70 Years. Gender(s): Female.

Criteria:

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

Institut Gustave Roussy, Villejuif F-94805, France; Recruiting
Eric Deutsch, MD, Phone: 33-1-4211-4339

Starting date: April 2008
Last updated: January 27, 2010