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

Cervical Cancer Clinical Trial

— HPV-RX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02515877
• Other study ID #: 2007-005505-21
• Secondary ID: 2007/1297
• Status: Completed
• Phase: Phase 1
• First received: August 3, 2015
• Last updated: June 8, 2016
• Start date: January 2008
• Est. completion date: April 2013

Study information

• Verified date: June 2016
• Source: Gustave Roussy, Cancer Campus, Grand Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. 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.

2. Detection of the virus genome of HPV positive on the primary tumor.

3. General state ECOG performance status 0-1.

4. 18 </ = age </ = 70 years.

5. PN> 2000 / mm3

6. hemoglobin> 9 g/l after transfusion if necessary .

7. platelets > 100 000 / mm3

8. Serum creatinine <1.5 upper limit of normal.

9. Liver function tests (SGOT, SGPT, alkaline phosphatase and bilirubin) <1.5 upper limit of normal.

10. Life expectancy> 3 months.

11. Systematic Beta HCG Dosage for premenopausal women.

12. Informed consent signed after informing the patient.

13. Proteinuria <2g / L (200mg / dL) and creatinine clearance of> / = 55 ml / min.

Exclusion Criteria:

1. Other histological types of cervix tumor than those mentioned in the inclusion criteria.

2. Search of viral sequences on the negative HPV tumor diagnosis.

3. History of cancer other than basal cell carcinoma.

4. Pre-treatment with radiotherapy or chemotherapy.

5. Ongoing pregnancy.

6. History or active psychiatric illness.

7. Nephropathy whatever the grade.

8. Infection scalable.

9. Active infection or other serious underlying pathology may prevent the patient receiving the treatment (in particular hepatic or cardiac).

10. Inclusion in another clinical trial protocol with an experimental molecule (during the study or within one month before inclusion).

11. Inability to submit to medical monitoring study for geographical, social or psychological.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Radiation:
• External radiotherapy + curietherapy
External radiotherapy: 45 Gy in 5 weeks Curietherapy: 15Gy

Drug:
• Vistide
VISTIDE® (mg/kg) Level 1: 1mg/kg Level 2: 2,5 mg/kg Level 3: 5 mg/kg Level 4: 6,5 mg/kg
• Carboplatin
AUC= 2,5 (Calvert formula)

Locations

Country	Name	City	State
France	Gustave Roussy Cancer Campus Grand Paris	Villejuif	Val de Marne

Sponsors (2)

Lead Sponsor	Collaborator
Gustave Roussy, Cancer Campus, Grand Paris	National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity		Assessed every week after inclusion up to 10 weeks	Yes
Secondary	Efficacy Using RECIST criteria	Using RECIST criteria	Assessed 14 weeks after inclusion	No