Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

All Drugs and Chemicals

Antineoplastic Agents

Valproic Acid

Topoisomerase I Inhibitors

Enzyme Inhibitors

Neurotransmitter Agents

All patients enrolled in the Phase II will be treated with Valproic Acid (VPA) and Karenitecin using the dosing schedule determined to be the Maximum Tolerated Dose (MTD) in Phase I.

Karenitecin

Adil Daud, M.D.

This is a Phase I study looking at the combination of Valproic Acid (VPA) and Karenitecin to treat patients with metastatic malignant melanoma. We will find the dose-limiting toxicity (DLT) and the highest dose (maximum tolerated dose) of this combination treatment that has acceptable side effects and recommend a Phase II dose level.

There will be seven escalating doses of Valproic acid and one dose escalation step of Karenitecin. Each patient shall receive one cycle of Karenitecin alone (cycle 1 days 1 - 5) followed by the same dose of Karenitecin given in combination with VPA (cycle 2 days 1-7). Patients will receive oral VPA in divided doses for 5 days and Karenitecin starting on the 3rd day every 3 weeks (a treatment cycle).

Treatment will continue until progression of disease or an unacceptable level of toxicity. After 2 cycles of treatment there will be the first efficacy evaluation or restaging of the disease. In the absence of disease progression and if there is continued safety and tolerability, treatment may continue.

Treatment cycles are every 3 weeks and there are 17 study visits in all.

During Phase I subjects will receive one cycle of Karenitecin alone (cycle 1 days 1-5) and then combination therapy with VPA + Karenitecin (cycle 2 days 1-7)followed by oral VPA in divided doses for 5 days and Karenitecin starting the third day (days 3-7) every 3 weeks. After 2 cycles of treatment there will be the first efficacy evaluation or restaging of the disease.

Dose escalations will continue until unacceptable dose limiting toxicity (DLT) occurs, then dose escalation will be stopped and the previous dose level will be explored. In each dose level, participants will undergo pharmacokinetic (PK) sampling to determine blood levels. The melanoma skin lesions will also be biopsied to measure the effect of the combination therapy.

All patients enrolled in the Phase II will be treated with VPA and Karenitecin using the dosing schedule determined to be the MTD in Phase I. In the absence of disease progression and if there is continued safety and tolerability, treatment may continue in consecutive 3 week cycles.

Phase I/II Trial of Valproic Acid and Karenitecin for Melanoma

Phase I/II Trial of Valproic Acid and Karenitecin for Metastatic Malignant Melanoma

BioNumerik Pharmaceuticals, Inc.

H. Lee Moffitt Cancer Center and Research Institute

Breast Neoplasms

Breast Diseases

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.

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.

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

Placebo

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.

Valproic Acid (VPA)

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

Questionnaires

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

Pill Diary

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.

Drainage Diary

Wendy A. Woodward, MD, PHD

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.

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.

If you are in Group 2, you will take VPA 3 times a day for a total of 10 weeks while an indwelling pleural catheter drains pleural fluid.

Study Drug Administration:

Within 48 hours of collection of baseline fluid, all study participants will take either placebo or VPA capsules 3 times a day by mouth with food. If you tolerate the starting dose well and the study doctor thinks it is in your best interest, your dose level will be doubled. You may be contacted at a later time by telephone to discuss how you are doing with the medicine. If your doctor feels your dose should be doubled, he/she will talk to you about it at this time.

Neither you nor the study staff will know if you are receiving the study drug or the placebo. However, if needed for your safety, the study staff will be able to find out what you are receiving.

You will be given a pill diary to record the time you take each dose. You will need to bring the diary with you to every clinic visit.

The fluid drained from the catheter will be collected and studied to see if the how the VPA is working and how it may affect the time you will need to have an indwelling pleural catheter.

You will also be asked to keep a daily diary of drainage with the date and amount of fluid drained each day at home. You will bring the drained fluid from the day before to each clinic visit to give to the research team. You will be given special containers to store the drained fluid. You will only save fluid from the day before each clinic visit. On the other days you will write down the amount of drained fluid that was collected, then you can throw away the fluid. You must bring the daily drainage diary to each clinic visit.

Study Visits:

At Weeks 2, 6, and 10 while you are receiving the study drug:

* You will have a complete physical exam including weight and vital signs and a medical history.
* You will complete the same questionnaires that you completed at screening.
* Your performance status will be recorded.
* Blood (about 2 tablespoons) will be drawn for routine tests.
* You will have a chest X-ray to check the status of the disease.

At Week 10 only, you will have a computed tomography (CT) scan of the chest to check the status of the disease.

Length of Study:

You will be taken off study after the indwelling pleural catheter has been removed. You will no longer be able to take part in this study if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your active participation in this study will be over after Week 10.

Follow-Up Medical Record Review:

After the 10 week visit the study personnel will continue to review your medical record to learn when the indwelling pleural catheter was removed. Your medical record information will continue to be reviewed for up to 5 years.

This is an investigational study. VPA is FDA approved and commercially available for the treatment of epileptic seizures and mania in bipolar disorder. VPA use in patients using pleural catheters is for research purposes only.

Up to 76 patients will take part in this study. All will be enrolled at MD Anderson.

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

Randomized Phase II Double Blind Study of Valproic Acid (VPA) vs Placebo to Shorten Time of Indwelling Pleural Catheter

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.

Inflammatory Breast Cancer Network Foundation

M.D. Anderson Cancer Center

Of the 3 participants started, only 1 completed with the other 2 withdrawing before treatment 1 withdrew and 1 screen failure. The protocol was terminated early.

Group 1 will take placebo 3 times a day for 10 weeks while an indwelling pleural catheter drains pleural fluid.

Group 1

Group 2 will take valproic acid (VPA) 3 times a day for a total of 10 weeks while an indwelling pleural catheter drains pleural fluid.

Group 2

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Wendy Woodward, PHD/ Professor, Radiation Oncology Department

Study terminated early with single patient leaving low accrual with insufficient data for analysis

Time to Pleural Catheter Removal

Overall Study

Symptoms and General Pathology

Blood and Lymph Conditions

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

Precancerous Conditions

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Cytarabine

Azacitidine

Decitabine

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

5-Azacytidine (5-Aza) 75 mg/m\^2 subcutaneously daily + Valproic Acid (VPA) 50 mg/m\^2 orally daily, each for 7 days

Low-Dose Ara-C 20 mg twice daily subcutaneously for 10 days.

75 mg/m\^2 daily for 7 days (days 1-7) via subcutaneous injection.

5-Azacytidine

20 mg twice daily via subcutaneous injection for 10 days.

Ara-C

Guillermo Garcia-Manero, MD

Primary Objective:

1. To evaluate whether 5 azacytidine (5-aza)/valproic acid (VPA) or low dose ara-C produces longer event free survival time in patients age \> or = 60 years with untreated Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) who are typically ineligible for, or not placed on, studies of new agents.

Secondary Objective:

1. To evaluate whether pre-treatment methylation/acetylation status in AML/MDS blasts predicts response to either therapy or whether the ability of the 5 azacytidine + valproic acid combination to induce demethylation or acetylation parallels response.

5-aza is a chemotherapy drug with activity in leukemia and MDS. Researchers hope that VPA will increase the effects of 5-aza. Low-dose Cytarabine (ara-C) is considered the standard of care for the treatment of leukemia and MDS in older patients not eligible for other therapies.

Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have blood drawn (about 2 teaspoons) for routine tests. You will also have a bone marrow biopsy and aspiration performed. To collect a bone marrow biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive 5-aza and VPA. Participants in the other group will receive ara-C alone. At first, there will be an equal chance of being assigned to either group. As the study goes along, however, the chance of being assigned to the treatment that has worked best so far will increase.

Participants in the 5-aza and VPA group will receive 5-aza as an injection under the skin once a day for 7 days in a row. On these same 7 days, participants in this group will also take VPA by mouth twice a day or 3 times a day based on your weight. Seven (7) days is considered 1 treatment cycle. Both drugs will be taken at the same time. Cycles will be repeated every 4 to 6 weeks.

Participants in the ara-C group will receive ara-c twice a day as an injection under the skin for 10 days (1 cycle). Cycles will be repeated every 4 to 6 weeks.

You will be monitored with routine blood tests (about 1-2 teaspoons each time) 2-3 times a week during this study.

You may receive up to 12 cycles of therapy. You may be taken off study early if the disease gets worse or intolerable side effects occur.

Once you go off study, you will have standard follow-up as is required by your primary physician.

This is an investigational study. 5-aza is approved by the FDA for MDS. VPA is approved by the FDA for epilepsy. Their use together in this study is experimental. Ara-C is approved for acute myelogenous leukemia. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.

Azacytidine With Valproic Acid Versus Ara-C in Acute Myeloid Leukemia (AML)/ Myelodysplastic Syndrome (MDS) Patients

A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies

Patient response defined by: Death, Resistant to Therapy \[no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses\], or Relapse.

5-Aza + VPA

Low-Dose Cytarabine (Ara-C) 20 mg twice daily subcutaneously for 10 days.

Age Continuous

Guillermo Garcia-Manero, MD / Associate Professor

Death

Resistant to Therapy

Relapse

The analysis was per intention to treat. One participant was inevaluable for response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I/II Trial of Valproic Acid and Karenitecin for Melanoma	NCT00358319	Malignant Melan...	Karenitecin Valproic Acid	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Study of Valproic Acid (VPA) vs Placebo to Shorten Time of Indwelling Pleural Catheter	NCT01900730	Breast Cancer	Placebo Valproic Acid (... Questionnaires Pill Diary Drainage Diary	18 Years -	M.D. Anderson Cancer Center
Azacytidine With Valproic Acid Versus Ara-C in Acute Myeloid Leukemia (AML)/ Myelodysplastic Syndrome (MDS) Patients	NCT00382590	Acute Myelogeno... Myelodysplastic... Leukemia	5-Azacytidine Ara-C Valproic Acid (...	60 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for valproic acid (vpa)