Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer

NCT00404326 | Completed Phase 2

• 1 other identifier: 005/013/ICI
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The current standard for locally advanced cervical cancer is concurrent cisplatin-based chemotherapy, however, the treatment results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the radiation and chemotherapy effects. Objective. To determine response rate, safety and biological effects of hydralazine and magnesium valproate when added to cisplatin chemoradiation. Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase the clinical complete response rate to 95% as compared to 75% as seen in historical controls treated with cisplatin chemoradiation in FIGO stage IIIB patients. Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical carcinoma with no previous treatment will be included. Patients will be typed for acetylator status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at 40mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy). Clinical response rate, safety and transcriptome changes will be analyzed.

Conditions

Cervical Cancer

Keywords

Cervical carcinoma; Epigenetic therapy; Hydralazine; Valproate; Microarray analysis

Outcome Measures

Primary Outcomes (2)

• Clinical Response

• Safety

Secondary Outcomes (4)

• Gene expression profiling

• Global DNA methylation

• HDAC activity

• Plasma levels hydralazine and valproic acid

Interventions

Hydralazine and magnesium valproate DRUG

Punch biopsy of the primary tumor PROCEDURE

Eligibility Criteria

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

You may qualify if:

• informed consent, histological diagnosis of cervical carcinoma (epidermoid, adenoesquamous and adenocarcinoma), clinical stage III B, untreated, aged 18-70 years, performance status 0-2 according to ECOG classification, and adequate liver, hematological and renal function, as defined by: hemoglobin \>10 g/L, leukocytes \>4000/mm3, platelets \>100 000mm3; normal creatinine value and creatinine clearance \>60 mL/min; total bilirubin \< 1.5 upper normal limit value; no evidence of systemic disease or para-aortic lymph node involvement.

Sponsors & Collaborators

• National Institute of Cancerología: lead
• National Council of Science and Technology, Mexico: collaborator
• Psicofarma, S.A. De C.V.: collaborator

Study Sites (1)

National Institute of Cancerologia

Mexico City, TLALPAN, 14080, Mexico

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Hydralazine; Valproic Acid

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)

Phthalazines; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Alfonso Duenas-Gonzalez, MD, PhD.

  National Institute of Cancerologia, Mexico

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: November 25, 2006
• First Posted: November 28, 2006
• Study Start: May 1, 2005
• Study Completion: November 1, 2006
• Last Updated: November 28, 2006

Record last verified: 2006-11

Locations

ME (1)