Study of Valproic Acid (VPA) vs Placebo to Shorten Time of Indwelling Pleural Catheter

NCT01900730 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2011-0930NCI-2014-01196
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

Breast cancer; Metastatic; Indwelling pleural catheter; Valproic acid; VPA; Depakene; Placebo; Pill diary; Drainage diary; Questionnaires; Surveys

Outcome Measures

Primary Outcomes (1)

• Time to Pleural Catheter Removal

  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.

  10 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Behavioral: Questionnaires; Behavioral: Pill Diary; Behavioral: Drainage Diary

Valproic Acid (VPA)

EXPERIMENTAL

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.

Drug: Valproic Acid (VPA); Behavioral: Questionnaires; Behavioral: Pill Diary; Behavioral: Drainage Diary

Interventions

Placebo DRUG

Patient takes placebo capsule 3 times a day by mouth for 10 weeks.

Placebo

Valproic Acid (VPA) DRUG

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.

Also known as: Depakene

Valproic Acid (VPA)

Questionnaires BEHAVIORAL

Questionnaires completed at baseline, weeks 2, 6, and 10.

Also known as: Surveys

Placebo; Valproic Acid (VPA)

Pill Diary BEHAVIORAL

Patient given a pill diary to record the time each dose taken.

Placebo; Valproic Acid (VPA)

Drainage Diary BEHAVIORAL

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.

Placebo; Valproic Acid (VPA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Inflammatory Breast Cancer Network Foundation: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Valproic Acid; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Results Point of Contact

• Title: Dr. Wendy Woodward, PHD/ Professor, Radiation Oncology Department
• Organization: UT MD Anderson Cancer Center

wwoodward@mdanderson.org

713-563-8481

Study Officials

• Wendy A. Woodward, MD, PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2013
• First Posted: July 16, 2013
• Study Start: July 31, 2014
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: February 25, 2020
• Results First Posted: February 25, 2020

Record last verified: 2020-02

Locations

US (1)