Phase III Clinical Trial: "Evaluation of the Combination of TRANSKRIP ® Plus Carboplatin and Paclitaxel as First Line Chemotherapy on Survival of Patients With Recurrent - Persistent Cervical Cancer
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 入组人数
- 230
- 试验地点
- 1
- 主要终点
- Overall survival
研究概览
简要总结
The purpose of this study is to determine the efficacy and safety the combination of TRANSKRIP ® vs placebo plus Carboplatin/Paclitaxel as first line treatment in patients with recurrent-persistent cervical cancer.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Operating status ECOG: 0-2
- •Negative pregnancy test or reproduction potential is zero, determined either by surgery, radiation or menopause, or mitigated with the use of some approved contraceptive method (IUD or hormonal contraceptive during the study and at least 3 months after the study).
- •Patients with histological diagnosis of persistent/recurrent cervical cancer, local and/or systemic, with disease measurable by physical examination and TAC. REQUIRED confirmation by biopsy of the recurrence or, persistence only if: lesion is single, less than 2 cm and/or has no sharp edges.
- •Chemo-radiotherapy to pelvis or pelvis plus extended fields (may have received concomitant chemotherapy as a radiosensitizer) provided it is within 90 days from the last application and the secondary radiation acute effects have disappeared.
- •Hemoglobin equal or greater than 9 g/L. (allowed transfusion prior to treatment to reach this hemoglobin level).
- •Leukocytes greater or equal to 4000/mm
- •Platelets equal or greater to 100 000 mm
- •Hepatic: Total bilirubin up to 1.5 times normal value, albumin equal or greater to 2: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) lower or equal to 2.5 times the regular superior limit.
- •Renal: Normal creatinine. If high, the extent debugging must be greater than 60 mL/min.
- •With the exception of alopecia, patients should have resolution of all acute toxic effects of any prior surgery, radiotherapy or chemotherapy, such effects qualified according to the Common Toxicity Criteria (CTC version 3.0) from the National Cancer Institute (NCI), or within the limits shown in laboratory parameters mentioned above.
- •Be willing and able to comply with the programmed visits, the treatment plan and laboratory tests.
- •The ability to understand the nature of the study and give a report written consent.
排除标准
- •Small cell and/or neuroendocrine cervical cancer.
- •History of allergy to hydralazine, magnesium valproate or sulfa.
- •Any disease of collagen present (Systemic Lupus Erythematosus (SLE), Rheumatoid arthritis (RA), etc), or history of the same.
- •Recent or past condition of symptomatic postural hypotension diagnosed by a clinician.
- •Secondary heart failure to aortic stenosis or any other condition where a vasodilator is contraindicated.
- •Recent or past condition of active disease of the central nervous system, including seizures.
- •Previous or current use of magnesium valproate and/or any other anticonvulsive.
- •Pregnant patients or nursing.
- •Prior cancer within the last 5 years or in presence of a second primary tumor (except carcinoma of the cervix in situ or basal cell carcinoma of the skin adequately treated).
- •Use of any of the research agents in the month prior to enrollment in this study.
- •Serious concomitant systemic disorders incompatible with the study at the discretion of the investigator.
- •Recently receiving another onco-specific treatment research.
- •The recently or previously diagnosed hypertension and controlled with any antihypertensive or a combination of them (provided that they do not include hydralazine) WON'T be an exclusion criteria.
- •Criteria Treatment Interruption
- •A patient will be discontinued from the study under the following circumstances.
- •If there is evidence of disease progression.
- •Unacceptable toxicity.
- •If the clinician considers that a change of therapy will be for the best interest of the patient.
- •If the patient requests the discontinuation.
- •If a patient gets pregnant or does not use an adequate birth control (for patients able to conceive).
研究组 & 干预措施
Hydralazine/Magnesium valproate + QT
This group will receive TRANSKRIP® (Hydralazine/Magnesium valproate) + Carboplatin plus Paclitaxel
干预措施: Hydralazine/Magnesium (Drug)
placebo + QT
This group will receive placebo + Carboplatin plus Paclitaxel
干预措施: Placebo (Drug)
Hydralazine/Magnesium valproate + QT
This group will receive TRANSKRIP® (Hydralazine/Magnesium valproate) + Carboplatin plus Paclitaxel
干预措施: Paclitaxel (Drug)
Hydralazine/Magnesium valproate + QT
This group will receive TRANSKRIP® (Hydralazine/Magnesium valproate) + Carboplatin plus Paclitaxel
干预措施: Carboplatin (Drug)
placebo + QT
This group will receive placebo + Carboplatin plus Paclitaxel
干预措施: Paclitaxel (Drug)
placebo + QT
This group will receive placebo + Carboplatin plus Paclitaxel
干预措施: Carboplatin (Drug)
结局指标
主要结局
Overall survival
时间窗: 24 months
patient´s survival since inclusion in the study until final event of death.
次要结局
- Objective Response(6 months)
- Toxicity(7 months)
- Quality of life(24 months)
- Progression free survival(24 months)
研究者
Lucely Cetina Pérez
MD. MSc.
National Institute of Cancerología