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A Phase II Study of Epigenetic Therapy With Hydralazine and Magnesium Valproate to Overcome Chemotherapy Resistance in Refractory Solid Tumors

Phase 2
18 Years
Not Enrolling
Refractory Solid Tumors

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Trial Information

A Phase II Study of Epigenetic Therapy With Hydralazine and Magnesium Valproate to Overcome Chemotherapy Resistance in Refractory Solid Tumors

Eligible patients after signing informed consent will undergo study evaluation and
acetylation status typing before being treated. Patients will begin treatment (day -7) with
a daily dose of a slow-release formulation of hydralazine tablets containing either 182 mg
for rapid-acetylators or 83 mg for slow-acetylators and slow-release tablets containing
700mg of magnesium valproate at a dose of 40mg/Kb t.i.d. Both hydralazine and magnesium
valproate will be administered from day -7 until the last day of the last chemotherapy
cycle. Chemotherapy will initiate at day 1 (after seven days of being taken hydralazine and
magnesium valproate) with the same pre-study protocol regimen at which patients showed tumor
progression. Toxicity will be evaluated after each course of chemotherapy. Response will be
evaluated at the third course of chemotherapy. Promoter of selected genes will be evaluated
by methylation-specific PCR in serum DNA before and after 7 days of treatment with
hydralazine and valproate.

Inclusion Criteria:

- Aged18 years and older.

- Histologically proven malignant solid tumors who were receiving their second, third
or fourth line of palliative chemotherapy and who showed at the second or third
course progressive disease as their maximum response according to the RECIST criteria
or to the IGCG CA125 criteria in case of ovarian cancer patients.

- Measurable disease defined by 1 of the following criteria: Any unidimensional
measurable lesion ≥ 10 mm by standard MRI or CT scan for solid tumors; or at least 1
non-measurable lesion that is evaluable by nuclear medicine, tumor markers, or other
reliable measures.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2; Absolute leukocyte
count (≥4000/mm3), platelets ≥100,000/mm3, hemoglobin ≥9.0 g/dL; total bilirubin,
aspartate amino transferase (AST) and alanine amino transferase (ALT) <1.5 the upper
normal limit (UNL), creatinine ≤1.2 mg/dL or a calculated creatinine clearance of ≥60

- Life expectancy of more than three months,

- Written informed consent.

Exclusion Criteria:

- History of allergy to hydralazine or valproate.

- Past or present condition of rheumatic disease, central nervous system disease, heart
failure from aortic stenosis and postural hypotension as diagnosed by a physician.

- Previous use of the experimental drugs (hydralazine and magnesium valproate)

- Pregnancy or breast-feeding.

- Uncontrolled systemic disease or infection.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Clinical benefit (complete response, partial response and stable disease)

Principal Investigator

Alfonso Duenas-Gonzalez, MD PhD

Investigator Role:

Study Director

Investigator Affiliation:

National Institute of Cancerologia


Mexico: Ethics Committee

Study ID:




Start Date:

September 2005

Completion Date:

October 2006

Related Keywords:

  • Refractory Solid Tumors
  • Hydralazine
  • Magnesium Valproate
  • Chemotherapy resistance
  • Epigenetic therapy
  • Neoplasms