Evaluation of TRANSKRIP ® Plus Chemotherapy in Recurrent-Persistent Cervical Cancer

HYPOTHESIS: It is estimated that adding TRANSKRIP ® to the chemotherapy an increase will occur in the survival of at least 3.6 months superior compared to the patients receiving only QT (17.9 months for TRANSKRIP plus QT and 14.3 months for QT, i.e. a 20% of difference).

Sample size: Data from GOG (Gynecologic Oncology Group) 240 study was used to define it where at 36 months the survival rate was 39.5% for the control group. Losses of 20%, 95% α, 80% β, among groups of 1 ratio and a better 20% survival in the experimental group were considered. From the above, 230 are included which will be in blocks of 10.

Study overview: In patients who meet the inclusion criteria an informed consent oral and written will be granted, once accepted screening test will be made to determine exclusion criteria (CAT, laboratories). If they meet all criteria, patients will be assigned to the following treatment groups:

Group A (115 patients): TRANSKRIP® (Hydralazine: 1 oral tablet every 24 hours, 182 mg for rapid acetylators, and 83 mg for low acetylators and Magnesium valproate: orally 30 mg/K weight every 8 hours) starting 1 week prior the first day of the QT Carboplatin based (5 area under curve (AUC) 1hour/day 1) plus Paclitaxel (175 175mg/m2/body surface (BS) 3hour/day 1) for every 21 days for 6 cycles.

Group B (115 patients): Placebo (orally) starting 1 week before the first day of the QT Carboplatin based (5 AUC 1hour/day 1) plus Paclitaxel (175 175mg/m2/BS 3hour/day 1) for every 21 days for 6 cycles.

Patients included in the study will be conducted to determine their acetylator genotype by polymerase chain reaction (PCR) sequencing N-acetyltransferase 2 (NAT2) gene, and blood samples will be sent to the central laboratory CIDAT S.A de C.V. Those with slow acetylation result will receive 83 mg/day of Hydralazine plus 30 mg/Kg/day of magnesium Valproate, patients with fast acetylation result will receive 182 mg/day of Hydralazine plus 30 mg/Kg/day of magnesium Valproate.

Assigning patients: Randomization will be automatically generated in a computer and with the randomization program; the list will be generated by the Contract Research Organization (CRO) hired for this study. The flasks will be labeled by the Alpharma Manufacturing Department, from the random list that identifies the treatment that every patient receives.

Dose adjustments: All patients should have, previous to the chemotherapy administration, an absolute neutrophil count \>1500/µL and platelets greater than 100,000/µL. If they have smaller numbers, treatment will be delayed during 1-2 weeks, until achieving these levels. There won't be dose adjustment of the chemotherapy. The chemotherapy dosage should not exceed the initial dose calculation, unless the patient has a weight change greater than 10% requiring the new dose calculation. A patient which cannot take the drug during 6 weeks since the last treatment should be discontinued from the study. In case of renal toxicity grade 3-4, the dosage of carboplatin will be decreased to 50%.