Randomized Phase II Double Blind Study of Valproic Acid (VPA) vs Placebo to Shorten Time of Indwelling Pleural Catheter
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Time to Pleural Catheter Removal
研究概览
简要总结
The goal of this clinical research study is to learn if receiving valproic acid (VPA) compared to a placebo can reduce the amount of time you will need to have an indwelling pleural catheter compared to the standard of care, which involves using an indwelling pleural catheter alone.
VPA is designed to stop cancer cells from dividing and maturing. This may cause the cancer cells to become less malignant and cause less pleural fluid production.
A placebo is not a drug. It looks like the study drug but is not designed to treat any disease or illness. It is designed to be compared with a study drug to learn if the study drug has any real effect.
详细描述
Baseline Fluid Collection:
Before receiving the study drug or the placebo, pleural fluid will be drained from your catheter to be compared to fluid collected later in the study.
Study Groups:
You will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups.
Group 1 will take a placebo 3 times a day for 10 weeks while an indwelling pleural catheter drains pleural fluid.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with symptomatic pleural effusion requiring the presence of an IPC or new placement of an IPC.
- •Pathologic documentation of breast cancer.
- •Performance status 0 to 3 (ECOG scale).
- •Signed informed consent.
- •Subject must be female or male age 18 years or over.
- •At least one prior line of chemotherapy in the metastatic setting.
- •Positive effusion cytology.
排除标准
- •Other prior malignancy (except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer) from which the patient has been disease-free for at least two years.
- •Laboratory results sustained at: Neutrophils less than 1.5 × 109/L ; Serum bilirubin >1.5 x the upper limit of reference range (ULRR); Serum creatinine >1.5 x ULRR or creatinine clearance < 30 mL/minute (calculated by Cockcroft-Gault formula).
- •Patients with a history of existing hypercalcemia, hypocalcemia, hypermagnesemia or hypomagnesemia that is not corrected despite supplementation. Known Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULRR or alkaline phosphatase (ALP) >2 x ULRR, or > 4x ULRR if judged by the investigator to be related to liver metastases.
- •Serious underlying medical condition that would impair the ability of the patient to receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension or renal diseases.
- •Diagnosis of an infection requiring IV antibiotics 14 days prior to registration.
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
- •Women who are currently pregnant or breast feeding.
- •Known hypersensitivity to VPA, valproate sodium, disodium valproate, or any ingredient in the respective formulation.
- •Known urea cycle disorders based on history.
- •Known HIV infection based on history.
- •Active or recent pancreatitis (within last 6 months).
- •Any of the following interventions on the affected hemithorax: prior IPC, prior chest tube placement, history of chemical or mechanical pleurodesis, history of thoracotomy within 4 weeks and incompletely healed surgical incision before randomization.
- •Evidence of empyema or history of empyema of the affected hemithorax.
- •Non-correctable bleeding diathesis.
- •Clinical evidence of skin infection at the potential site of IPC placement.
- •Patients currently taking valproic acid.
- •History of hepatitis or liver disease.
- •The following drugs will not be administered concurrently with VPA: Carbapenem antibiotics; Clonazepam; Topiramate; Felbamate; Lorazepam; Barbiturates; Barbiturates; CarBAMazepine; ChlorproMAZINE; Ethosuximide; GuanFACINE; LamoTRIgine; MethylfolateOXcarbazepine; Paliperidone; Phenytoin; Primidone; Protease Inhibitors; Rifampin; Risperidone; Rufinamide; Salicylates; Temozolomide; Tricyclic Antidepressants; Vorinostat; Zidovudine.
- •History of seizures.
研究组 & 干预措施
Placebo
Patient takes placebo capsule 3 times a day by mouth for 10 weeks. Patient contacted by phone to assess tolerance and instruction to increase dose. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Placebo (Drug)
Placebo
Patient takes placebo capsule 3 times a day by mouth for 10 weeks. Patient contacted by phone to assess tolerance and instruction to increase dose. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Questionnaires (Behavioral)
Placebo
Patient takes placebo capsule 3 times a day by mouth for 10 weeks. Patient contacted by phone to assess tolerance and instruction to increase dose. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Pill Diary (Behavioral)
Placebo
Patient takes placebo capsule 3 times a day by mouth for 10 weeks. Patient contacted by phone to assess tolerance and instruction to increase dose. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Drainage Diary (Behavioral)
Valproic Acid (VPA)
Patients initially receive daily oral VPA 15 mg/kg/day divided in three doses. If patient tolerates the reduced dose for 10 consecutive days, then the VPA dose will increase to 30 mg/kg/day divided into three doses. Patients treated for 10 weeks. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Valproic Acid (VPA) (Drug)
Valproic Acid (VPA)
Patients initially receive daily oral VPA 15 mg/kg/day divided in three doses. If patient tolerates the reduced dose for 10 consecutive days, then the VPA dose will increase to 30 mg/kg/day divided into three doses. Patients treated for 10 weeks. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Questionnaires (Behavioral)
Valproic Acid (VPA)
Patients initially receive daily oral VPA 15 mg/kg/day divided in three doses. If patient tolerates the reduced dose for 10 consecutive days, then the VPA dose will increase to 30 mg/kg/day divided into three doses. Patients treated for 10 weeks. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Pill Diary (Behavioral)
Valproic Acid (VPA)
Patients initially receive daily oral VPA 15 mg/kg/day divided in three doses. If patient tolerates the reduced dose for 10 consecutive days, then the VPA dose will increase to 30 mg/kg/day divided into three doses. Patients treated for 10 weeks. Questionnaires completed at baseline, weeks 2, 6, and 10. Patient given a pill diary to record the time each dose taken. Patient completes daily diary of drainage with the date and amount of fluid drained each day at home. Drained fluid from the day before brought to each clinic visit to give to the research team.
干预措施: Drainage Diary (Behavioral)
结局指标
主要结局
Time to Pleural Catheter Removal
时间窗: 10 weeks
Primary outcome is time to pleural catheter removal because it is no longer needed to drain the pleura of fluid. Time to catheter removal measured from the date of placement of the catheter to the date it is removed. Cox (1972) proportional hazards regression used to model time to catheter removal as a function of treatment arm, cytology, and lung re-expansion, as well as other potential prognostic factors, including ECOG performance status, number of circulating tumor cells in peripheral blood and in pleural effusion.
次要结局
未报告次要终点