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

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

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.

Study Overview

• Status: Unknown
• Conditions: Cervical Cancer; Precancerous Condition
• Intervention / Treatment: Drug: carboplatin; Radiation: radiation therapy; Genetic: protein expression analysis; Other: laboratory biomarker analysis; Radiation: brachytherapy; Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Maximum tolerated dose of cidofovir

Collaborators and Investigators

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris
• Investigators: Eric Deutsch, MD, Gustave Roussy, Cancer Campus, Grand Paris

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Anticipated): October 1, 2009

Study Registration Dates

• First Submitted: December 18, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (Estimate): December 19, 2008

Study Record Updates

• Last Update Posted (Estimate): January 28, 2010
• Last Update Submitted That Met QC Criteria: January 27, 2010
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: cervical squamous cell carcinoma; stage III cervical cancer; stage IVA cervical cancer; stage IB cervical cancer; cervical adenocarcinoma; human papilloma virus infection; stage II cervical cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Precancerous Conditions; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antineoplastic Agents; Carboplatin; Cidofovir
• Other Study ID Numbers: CDR0000626799; IGR-CSET-2007/1297; IGR-HPV-RX; INCA-RECF-0813; EUDRACT-2007-005505-21