Modulation of the Expression of Papillomavirus (HPV) Oncoproteins to Major the Radiosensitivity: Trial Combining an Antiviral Agent VISTIDE and Radiochemotherapy in Cervical Cancers

NCT02515877 | Completed Phase 1

• 2 other identifiers: 2007-005505-212007/1297
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The treatment of cervical tumors depends on the stage of the disease. In advanced forms (nodal and / or local extension to the vagina and / or parameters) , radiotherapy associated with curietherapy , plays a major role. Until recently this association was the standard treatment for advanced stage uterine cancer. With this combination, rates of local failures (evolutionary prosecution and local recurrences) were 20 to 50% in stages IIb and 50-75 % for stage III. More than 50% for patients with a cervical cancer locally advanced (FIGO stages II / IV) . The standard treatment, external radiotherapy followed by curietherapy allows expect survival rates at 5 years for approximately 30-45 %. For ten years, numerous studies have evaluated the addition of concurrent chemotherapy to radiotherapy in cancer of the cervix. More than 19 randomized trials have been published. A meta-analysis of these trials was undertaken to assess the role of radiochemotherapy in cancers of the cervix. The first meta-analysis published by the Cochrane Collaborative Group, taking into account 4580 patient, shows an improvement in survival, both in terms of progression free survival and overall survival for patients treated with radio chemotherapy respectively 16% and 12 % (p \< 0.0001). The rate of metastasis is also decreased (p \< 0.0001). Survival rates were significantly better when platinum salt was used ( p \< 0.0001 ) . However, no clinical benefit of chemoradiotherapy has been demonstrated for tumors stages \[1, 2\] locally advanced, possibly due to small number of patients. The investigators have previously shown that antiviral agents used in preclinical models, Cidofovir® causes the selective radiosensitization of cells infected by the papillomavirus (HPV). This trial proposes to study a new concept to increase radiochemotherapy efficiency: the modulation of the expression of viral oncoproteins HPV virus by an antiviral agent.

Conditions

Cervical Cancer

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicity

  Assessed every week after inclusion up to 10 weeks

Secondary Outcomes (1)

• Efficacy Using RECIST criteria

  Assessed 14 weeks after inclusion

Study Arms (1)

Radiotherapy + Vistide + Chemoterapy

EXPERIMENTAL

Radiation: External radiotherapy + curietherapy; Drug: Vistide; Drug: Carboplatin

Interventions

External radiotherapy + curietherapy RADIATION

External radiotherapy: 45 Gy in 5 weeks Curietherapy: 15Gy

Radiotherapy + Vistide + Chemoterapy

Vistide DRUG

VISTIDE® (mg/kg) Level 1: 1mg/kg Level 2: 2,5 mg/kg Level 3: 5 mg/kg Level 4: 6,5 mg/kg

Radiotherapy + Vistide + Chemoterapy

Carboplatin DRUG

AUC= 2,5 (Calvert formula)

Radiotherapy + Vistide + Chemoterapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with cervix cancer : Squamous cell carcinoma or adenocarcinoma of stage IB2\> 4 cm, II, III or IVA (International Federation of Gynecology Obstetrics, regardless of pelvic lymph node status (optional surgical exploration) without paraaortic metastasis.
• Detection of the virus genome of HPV positive on the primary tumor.
• General state ECOG performance status 0-1.
• \</ = age \</ = 70 years.
• PN\> 2000 / mm3
• hemoglobin\> 9 g/l after transfusion if necessary .
• platelets \> 100 000 / mm3
• Serum creatinine \<1.5 upper limit of normal.
• Liver function tests (SGOT, SGPT, alkaline phosphatase and bilirubin) \<1.5 upper limit of normal.
• Life expectancy\> 3 months.
• Systematic Beta HCG Dosage for premenopausal women.
• Informed consent signed after informing the patient.
• Proteinuria \<2g / L (200mg / dL) and creatinine clearance of\> / = 55 ml / min.

You may not qualify if:

• Search of viral sequences on the negative HPV tumor diagnosis.
• History of cancer other than basal cell carcinoma.
• Pre-treatment with radiotherapy or chemotherapy.
• Ongoing pregnancy.
• History or active psychiatric illness.
• Nephropathy whatever the grade.
• Infection scalable.
• Active infection or other serious underlying pathology may prevent the patient receiving the treatment (in particular hepatic or cardiac).
• Inability to submit to medical monitoring study for geographical, social or psychological.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• National Cancer Institute, France: collaborator

Study Sites (1)

Gustave Roussy Cancer Campus Grand Paris

Villejuif, Val de Marne, 94805, France

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Brachytherapy; Cidofovir; Carboplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Cytosine; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2015
• First Posted: August 5, 2015
• Study Start: January 1, 2008
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: June 9, 2016

Record last verified: 2016-06

Locations

FR (1)