Study of Valproic Acid (VPA) vs Placebo to Shorten Time of Indwelling Pleural Catheter
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Placebo; Valproic Acid (VPA); Questionnaires; Pill Diary; Drainage Diary
Intervention description: Patient takes placebo capsule 3 times a day by mouth for 10 weeks.; 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.
Intervention MeSH terms: Valproic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Metastatic; Indwelling pleural catheter; Valproic acid; VPA; Depakene; Placebo; Pill diary; Drainage diary; Questionnaires; Surveys

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with symptomatic pleural effusion requiring the presence of an IPC or new
             placement of an IPC.

          2. Pathologic documentation of breast cancer.

          3. Performance status 0 to 3 (ECOG scale).

          4. Signed informed consent.

          5. Subject must be female or male age 18 years or over.

          6. At least one prior line of chemotherapy in the metastatic setting.

          7. Positive effusion cytology.

        Exclusion Criteria:

          1. 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.

          2. 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).

          3. 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.

          4. Serious underlying medical condition that would impair the ability of the patient to
             receive protocol treatment, specifically cardiac diseases, uncontrolled hypertension
             or renal diseases.

          5. Diagnosis of an infection requiring IV antibiotics 14 days prior to registration.

          6. Any psychological, familial, sociological or geographical condition potentially
             hampering compliance with the study protocol and follow-up schedule.

          7. Women who are currently pregnant or breast feeding.

          8. Known hypersensitivity to VPA, valproate sodium, disodium valproate, or any ingredient
             in the respective formulation.

          9. Known urea cycle disorders based on history.

         10. Known HIV infection based on history.

         11. Active or recent pancreatitis (within last 6 months).

         12. 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.

         13. Evidence of empyema or history of empyema of the affected hemithorax.

         14. Non-correctable bleeding diathesis.

         15. Clinical evidence of skin infection at the potential site of IPC placement.

         16. Patients currently taking valproic acid.

         17. History of hepatitis or liver disease.

         18. 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.

         19. History of seizures.