Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Carboplatin

Azacitidine

Decitabine

Valproic Acid

Antimetabolites

Enzyme Inhibitors

Neurotransmitter Agents

Azacitidine 75 mg/m\^2 subcutaneous injection or by vein daily for 5 Days. Valproic Acid 40 mg/kg by mouth daily for 7 days. Carboplatin area under the curve (AUC) 2 by vein on Days 3 and 10 over 60 Minutes.

75 mg/m\^2 Subcutaneous Injection or by vein Daily for 5 Days.

AUC 2 by vein on Days 3 and 10 over 60 Minutes.

Gerald Falchook, MD

The goal of this clinical research study is to find out if giving azacitidine with valproic acid plus carboplatin can help control advanced cancer. The safety of this treatment will be studied as well. Researchers will also collect some extra blood samples for molecular marker studies (studies that may help researchers predict how participants respond to the combined therapy).

There were to be two phases of this study: a Phase 1 portion to find acceptable doses of the study drug combination, and a Phase 2 portion to study the response rates to the treatment schedule. The study did not proceed to the Phase 2 portion.

The Study Drugs:

Researchers want to see if the combination of azacitidine, carboplatin, and valproic may work better together to control advanced cancer.

* Azacitidine is designed to activate ("turn on") certain genes in cancer cells whose job is to fight tumors, which may also make azacitidine work better with other anti-tumor drugs.
* Carboplatin is designed to block the growth of cancer cells by stopping cell division, which may cause the cells to die.
* Valproic acid is an anti-seizure medication that may also have cancer-fighting abilities. This drug may be able to activate tumor-fighting genes, causing cancer cells to die.

Phase 1 (Dose Escalation) and Phase 2 (Treatment):

Participants will be enrolled on Phase 1 of the study in groups of 3. Each group will receive a different combination of the study drugs. If the first group of 3 tolerates the study drug combination well, the next group of 3 will be enrolled, and their dose(s) of carboplatin and/or valproic acid will be higher than the last group. Each new group will get a higher dose of carboplatin and/or valproic acid. If 1 of the 3 participants has a serious side effect at a certain dose level, 3 more participants may be added at that dose level to check the safety of the combination. If no more participants at that dose level have serious side effects, the next dose level will be tested. However, if a second participant has a serious side effect, then the dose level before that one will be considered the "maximum tolerated dose" (MTD). Once the MTD is found, participants will be enrolled on Phase 2 of the study.

Participants enrolled on Phase 2 were to be given the MTD level of the study drug combination; however, study did not progress to Phase 2.

Participants on both phases were to have the same treatment schedule and study tests performed. The only difference between Phase 1 and Phase 2 was to be the dose level of the study drug combination being given.

Study Treatment:

If eligible, participants received the study treatment on a 28-day treatment cycle.

On Day 1 of each cycle, they receive an injection of azacitidine just under the skin or by vein over 30 minutes once a day for 5 days in a row.

On Day 3 and Day 10 of each cycle, they receive carboplatin by vein over 60 minutes.

On Days 5-11 of each cycle, they take valproic acid by mouth once a day with or without food.

On Day 12 of each cycle, they may receive an injection of NeulastaTM (pegfilgrastim) just under the skin, depending on whether the study doctor thinks it is needed to help boost your white blood cell count.

On Days 13-28 of each cycle, they have a "rest period" from the study drugs before beginning a new 28-day cycle of treatment.

Study Visits:

At certain time points, they have the following tests/procedure performed during study visits:

On Day 5 and Day 11 of Cycles 1-3, about 1 tablespoon of blood drawn before treatment for molecular marker studies. These tests will be performed to look for a link between genetic characteristics and response to the study drug treatment.

Within the last 72 hours (3 days) of each cycle, blood drawn (about 1 tablespoon) and urine collected for routine tests. After the start of each cycle, blood drawn (about 1 tablespoon) once weekly for routine tests.

Within 7 days before starting each new cycle, evaluation to see if you may be experiencing any side effects.

After the end of every 2 cycles (about every 8 weeks), an x-ray and either a CT scan or an MRI scan to re-evaluate the cancer.

Length of Study:

Participants will continue to receive treatment on this study, as long as the disease does not get worse and you do not experience any intolerable side effects.

End-of-Treatment Visit:

Once treatment has ended for any reason, participants will come back for an end-of-treatment visit to have the following tests/procedures performed:

* You will have a complete physical exam.
* You will have urine collected and blood drawn (about 1 tablespoon) for routine tests.
* You may have a CT scan or an MRI scan to remeasure and re-evaluate the cancer.

Up to 65 patients were eligible to take part in this study. All were to be enrolled at M. D. Anderson. Study halted after Phase 1 without progressing to second phase.

Azacitidine and Valproic Acid Plus Carboplatin in Patients With Ovarian Cancer

Phase I Trial of Sequential Azacitidine and Valproic Acid Plus Carboplatin in the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer

Assessment of tumor response by palpation, plain x-ray, MRI, or CT scan to be obtained after the first cycle and the every 2 cycles after that (8 weeks).

Celgene Corporation

M.D. Anderson Cancer Center

Histone Deacetylase Inhibitors

Starting Dose 20 mg/m\^2 administered subcutaneously (under the skin), daily, for ten days (Days 1 -10) of every 4 Week Cycle.

Starting Dose 10 mg/Kg once daily by mouth, every day of 4 Week Cycle.

Razelle Kurzrock, MD

Primary Objective:

1. To evaluate side effects and maximum tolerated dose of azacitidine and valproic acid in patients with advanced cancer.

Secondary Objectives:

1. To perform a preliminary assessment of the histone acetylation and DNA methylation effects of this combination on peripheral blood mononuclear cells (PBMC).
2. To assess the clinical anti-tumor activity (objective response including complete and partial responses) of this combination in patients with advanced cancer, in a descriptive fashion.

Azacitidine is a new chemotherapy drug that is designed to destroy cancer cells at high doses. At low doses, it is designed to destroy some cancer cells as well as cause changes that may make cancer cells less harmful. Valproic acid is a drug that is used in every day practice in the treatment of seizures, migraine headache, and mood disturbance in bipolar disorders.

Before you can start receiving the study drug, 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 a complete physical exam, including routine blood tests (about 4 teaspoons). You may have to get either a CT scan or a MRI to measure your disease if you have not had one within 1 month. Women who are able to have children must have a negative blood-pregnancy test.

If you are found to be eligible to take part in this study, you will receive the study drug in "cycles." Cycles will generally be 4 weeks long but may be longer, depending on any side effects you experience from the azacitidine. During each cycle, you will receive azacitidine under the skin once each day for the first 10 days (Day 1 to Day 10). You will then have an 18-day break during which you will not receive azacitidine injections for the rest of the cycle. Additionally, you will take valproic acid pills by mouth, every day, starting the first day of the first cycle (Day 1 to Day 28). You will take valproic acid every day while on study without interruption.

The dose of azacitidine that you receive will depend on when you enroll in this study. You will be part of a study group "cohort" (6 patients will be enrolled in each cohort). All members of a cohort receive the same dose of azacitidine when they begin receiving the study drug. Each new cohort will receive a higher dose than the cohort before. The dose of azacitidine that you receive may be adjusted depending on how well you tolerate it. The starting dose of valproic acid is fixed for all the patients, but this dose may be adjusted by your physician based on the results of your blood work.

You will have a physical exam and blood tests (about 1 tablespoon each) every two weeks of the first two study drug cycles. For further cycles, you will have a physical exam and blood test only once a month. Your disease will be measured by CT scan or MRI after every 2 treatment cycles.

You may continue to receive the study drug on this study until your disease gets worse or intolerable side effects occur. After your participation in this study is over, you will receive follow-up care, as is standard of care for your disease.

This is an investigational study. The FDA has approved azacitidine for a blood disease known as myelodysplastic syndrome. Its use in this study is experimental. The valproic acid is a drug approved by the FDA for treatment of seizure, bipolar disorders, and migraine headaches. Up to 68 patients will take part in the study. All will be enrolled at M. D. Anderson.

Azacytidine and Valproic Acid in Patients With Advanced Cancers

Phase I Study of Low-Dose Hypomethylating Agent Azacitidine Combined With the Histone Deacetylase Inhibitor Valproic Acid in Patients With Advanced Cancers

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

Dermatologic Agents

Tretinoin

Keratolytic Agents

Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.

Start at 75 mg/m\^2 subcutaneously daily for 7 days.

5-Azacytidine (5-aza)

50 mg/kg daily by mouth for 7 days, same days as 5-aza.

45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3 of the administration of 5-aza and VPA.

All-Trans Retinoic Acid (ATRA)

Guillermo Garcia-Manero, MD

5-aza is a chemotherapy drug with activity in leukemia and myelodysplastic syndromes (MDS). Researchers hope that valproic acid (VPA) and all-trans retinoic acid (ATRA)will increase the effects of 5-aza. The goal of this clinical research study is to find the highest safe dose of valproic acid (VPA) that can be given in combination with 5-azacytidine (5-aza) and all-trans retinoic acid (ATRA) in the treatment of AML and MDS. The safety and effectiveness of this combination therapy will also be studied.

Additional blood and bone marrow samples will be requested. These samples will be used to evaluate the effect of the treatment on leukemic cells. In addition, any leftover blood and bone marrow samples that are collected at the start of the study and during the regularly scheduled evaluations to be sent for research studies. The research studies will examine changes in the blood and bone marrow cells that might help explain the causes of leukemia and MDS and how the combination of 5-aza, VPA, and ATRA works.

Recent studies have shown synergy between demethylating agents and histone deacetylase inhibitors. In my laboratory, we have developed in vitro models using HL-60 and MOLT4 leukemic cells to study the effects of the combination of decitabine (a 5-azacytidine analogue) and valproic acid. Valproic acid is an antiepileptic agent with histone deacetylase inhibitory capacity. These results indicate that the addition of valproic acid to decitabine has an additive effect on growth inhibition, induction of apoptosis, induction of p57KIP2 and p21CIP1 expression independent of cell cycle arrest. These results were dependent on the dose and duration of treatment but not on the sequence used. Based on this data, we developed a phase I/II study of the combination of decitabine and valproic acid (2003-0314) in patients with leukemia that has shown that valproic acid can be safely administered up to doses of 50 mg/kg orally for 10 days in combination with decitabine, and that this combination has significant activity in patients with relapsed/refractory AML and MDS. All-trans retinoic acid (ATRA) is a biological agent that has been shown to induce cell differentiation in leukemia cell lines and has significant clinical activity in acute promyelocytic leukemia with minimal toxicity. In vitro, the combination of ATRA with either a hypomethylating agent or a histone deacetylase inhibitor has been shown to restore ATRA sensitivity in resistant cells. More recently, a German group has reported that the combination of valproic acid and ATRA has activity in patients with MDS and an excellent toxicity profile. 5-azacytidine is a nucleoside analogue with hypomethylating activity that has been shown in a randomized study to benefit patients with MDS, including an improvement in quality of life. Based on this data, this agent was recently approved by the FDA for its use in patients with MDS, and has become the first line agent for patients with MDS that required therapy.

The objectives of the clinical trial are the following:

* To determine the maximal tolerated dose of valproic acid (VPA) in combination with 5-azacytidine (5-aza) and all-trans retinoic acid.
* To determine the clinical activity of the combination of 5-azacytidine, valproic acid and all-trans retinoic acid in patients with AML and MDS.
* To determine the in vivo molecular and biological effects of this combination. These will include analysis of changes in Deoxyribonucleic acid (DNA) methylation, histone modifications, and gene expression.

Phase II 5-Azacytidine Plus VPA Plus ATRA

Phase II Study of the Combination of 5-azacytidine With Valproic Acid and All-trans Retinoic Acid in Patients With High Risk Myelodysplastic Syndrome and Acute Myelogenous Leukemia

Clinical activity of combination defined as: Complete Response (CR), bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10\^9/L or more and platelet count of 100x10\^9 or more; Complete response without platelets (CRp), a complete response except for a platelet count less than 100x10\^9 and transfusion independent; and Bone Marrow (BM) Response, bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for (CR) or (CRp).

VPA + 5-aza + ATRA

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Guillermo Garcia-Manero, MD / Associate Professor

Number of Participants With Response

Overall Study

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin 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

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

Ethnicity (NIH/OMB)

Race (NIH/OMB)

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

Bevacizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Valproic acid administered at a dose of 5.3 mg/Kg/day on days 1 - 28. Depending on the calculated dose, patients will take capsules once or twice a day per mouth.

Bevacizumab administered at a dose of 2.5 mg/kg by vein every 2 weeks.

2.5 mg/kg by vein over 90 minutes every 2 weeks

Jennifer Wheler, MD

The goal of this clinical research study is to find the highest tolerable dose of bevacizumab in combination with valproic acid that can be given to patients with advanced cancer that has not responded to standard treatment or where there is no standard treatment for the disease. The safety of this drug combination will also be studied.

Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels. Valproic acid works the same was way as bevacizumab and is also used in the treatment of seizures, migraine headaches, and mood disturbances in bipolar disorders.

If you are found to be eligible to take part in this study, you will receive the study drugs as an outpatient. You will receive bevacizumab by vein over 90 minutes (for the first infusion) once every 2 weeks. Once the study doctor determines that you are able to tolerate the drug, it will be given over 60 minutes for the second infusion and then over 30 minutes for further infusions. Valproic acid will be given by mouth (capsule(s)) each day for 28 days. You will take valproic acid once or twice a day depending on your dose. Every 28 days is considered 1 cycle.

You will have blood drawn (about 2 teaspoons) and urine collected for routine tests every cycle, about every 1-2 weeks, so that researchers can monitor the safety of the study drugs. Once every 8 weeks you will have tumor markers tested as part of the routine blood draw. You will have a physical exam once a cycle.

You will have either a CT or MRI scan of the tumor about every 8 weeks to check the status (whether it is growing or shrinking) of the cancer. If your doctor thinks other tests are necessary he/she will discuss those with you.

You will continue to receive bevacizumab and valproic acid as long as the disease is considered stable. You will receive up to 12 cycles of the study drug. If the disease gets worse or you experience any intolerable side effects, you will be taken off this study.

You will have an end-of-study visit 28 days after your last dose of bevacizumab. At this visit, you will have a complete physical exam, including measurement of your vital signs and blood pressure. You will have a neurological exam, and blood (about 2 teaspoons) will be drawn for routine and tumor marker tests. You will be asked about any medications you may be taking and whether you have had any side effects. You will also be asked how well you are able to perform daily activities.

This is an investigational study. Bevacizumab and valproic acid are both FDA approved and commercially available. Their use together in this study is investigational and authorized for use in research only. Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.

Valproic Acid and Bevacizumab in Patients With Advanced Cancer

Phase I Study of Valproic Acid Given in Combination With Bevacizumab in Patients With Advanced Cancer to Determine Safety and Tolerability

Nervous System Diseases

Neoplasm Metastasis

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Neuroepithelial

Neuroepithelioma

Etoposide

Etoposide phosphate

Valproate Starting Dose of 10 mg/kg By Mouth Daily. Etoposide 25 - 50 mg/m\^2 By Mouth Daily.

Valproate

Tribhawan S Vats, MD

Primary Objective:

* Determine the interindividual range and median of individual maximum tolerated doses of valproic acid administered as one time evening dose in conjunction with a dose oral etoposide (50 mg/m2/day for children, but only 25mg/m2/day for adults to start) for four different age groups.

Secondary Objectives:

* Determine the qualitative and quantitative toxicity and reversibility of toxicity of valproic acid in conjunction with oral etoposide,
* To investigate the clinical pharmacokinetics of valproic acid when given in conjunction with oral etoposide,
* To describe quality of life of patients with relapsed, or progressive central and peripheral nervous system tumors when treated with oral valproic acid and etoposide,
* To observe and describe the response pattern of progressive central nervous system tumors treated with oral valproic acid and etoposide,
* To observe and describe event free survival time and overall survival time of patients with relapsed, or progressive central nervous system tumors when treated with oral valproic acid and etoposide,
* To determine if histone deacetylase activity and topoisomerase expression in lymphocytes of patients is related to valproic acid levels, and
* To determine, if the individual maximal tolerated dose (iMTD) depends on the initial performance status of the patient in the beginning of the treatment.

Study Drugs:

Etoposide is designed to block cell growth by breaking the DNA, which may cause the cells to die.

Valproic acid was first designed as an anti-seizure medication. It was also found to change cancer cells and make them more sensitive to etoposide.

Screening Tests:

Before you start treatment on this study, you will have "screening tests". These tests help your doctor decide if you are eligible to take part in this study.

* Your medical history will be reviewed.
* You will have a physical exam.
* You will be asked how well you are able to perform the normal activities of daily living (performance status evaluation).
* You will complete a questionnaire about your activities or daily living. The questionnaire will take about 5 to 10 minutes to complete.
* Blood (about 2-3 tablespoons) will be drawn for routine tests. This routine blood draw may include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.
* Urine may be collected to check for metabolic disease. This urine sample may include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative.
* You will have a magnetic resonance imaging (MRI) or computed tomography (CT) scan.
* If your doctor thinks it is necessary, you may have additional blood and/or urine tests.

Dose Escalation:

When you begin the study, you will begin receiving the lowest dose level of valproic acid. Every week, the dose will be increased. This will continue until the maximum tolerated dose (MTD) is found. Once the MTD is found, you will continue to receive that dose level of valproic acid while you are on study. However, if your doctor thinks it is necessary, this dose level could be lowered.

If you are a child (less than or equal to 18 years of age), the amount of etoposide that you take while on study will not change.

If you are an adult (more than 18 years of age), your will receive a low dose of etoposide while the MTD of valproic acid is being found. After the MTD of valproic acid is found, your dose of etoposide will be increased every week until the MTD is found. However, if your doctor thinks it is necessary, this dose level could be lowered.

Study Drug Administration:

You will receive valproic acid and etoposide every evening in pill form.

If you have difficulty swallowing the pills, etoposide can be given in the evening in liquid form. Valproic acid can be given in liquid form, divided in 2 doses per day, 1 in the morning and 1 in the evening.

Study Visits During Dose Escalation:

While your valproic acid or etoposide medication is being increased, every week you will have a physical exam and blood (about 2-3 tablespoons)and urine will be collected for routine tests.

Every other month, you will have CT or MRI scans to check the status of the disease. You may have these tests and procedures more often if your doctor thinks it is necessary.

Study Visits After Maximum Tolerated Dose (MTD):

Every month, you will have a physical exam, and blood (about 2-3 tablespoons) and urine will be collected for routine tests.

Every other month, you will have CT or MRI scans to check the status of the disease.

Every 6 months, a portion of the blood or urine collected for routine tests will be used for a pregnancy test for women who are able to have children.

-You may have these tests and procedures more often if your doctor thinks it is necessary.

Length of Study:

You may remain on study for up to 2 years. You will be taken off study if the disease gets worse or intolerable side effects occur.

End-of-Study Visit:

Once you are off study, you will have an end-of-study visit. At this visit, the following tests and procedures will be performed:

* You will have a physical exam.
* Blood (about 2-3 tablespoons) and urine will be collected for routine tests.
* If your doctor thinks it is necessary, you will have a CT or MRI to check the status of the disease.

Follow-Up:

Once you are off study, you will be contacted by telephone once a year to check the status of the disease. The phone call will take 2-3 minutes.

This is an investigational study. Etoposide is FDA approved and commercially available. Valproic acid is FDA approved and commercially available for the treatment of seizures. The use of these drugs together is investigational. Up to 120 patients will take part in this multicenter study. Up to 100 will be enrolled at M. D. Anderson.

Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases

Valproate (Valproic Acid) and Etoposide for Patients With Progressive, Relapsed or Refractory Neuronal Tumors and Brain Metastases

Anti-Infective Agents

Cytarabine

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

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.

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
Azacitidine and Valproic Acid Plus Carboplatin in Patients With Ovarian Cancer	NCT00529022	Solid Tumors	Azacitidine Valproic Acid Carboplatin	-	M.D. Anderson Cancer Center
Azacytidine and Valproic Acid in Patients With Advanced Cancers	NCT00496444	Advanced Cancer...	Azacitidine Valproic Acid	2 Years -	M.D. Anderson Cancer Center
Phase II 5-Azacytidine Plus VPA Plus ATRA	NCT00326170	Myelodysplastic... Acute Myelogeno...	5-Azacytidine (... Valproic Acid All-Trans Retin...	3 Years -	M.D. Anderson Cancer Center
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 and Valproic Acid in Patients With Advanced Cancers	NCT00496444	Advanced Cancer...	Azacitidine Valproic Acid	2 Years -	M.D. Anderson Cancer Center
Valproic Acid and Bevacizumab in Patients With Advanced Cancer	NCT00530907	Advanced Cancer	Valproic Acid Bevacizumab	-	M.D. Anderson Cancer Center
Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases	NCT00513162	Neuroectodermal... Brain Metastase... Advanced Cancer	Valproate Etoposide	-	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
Azacitidine and Valproic Acid Plus Carboplatin in Patients With Ovarian Cancer	NCT00529022	Solid Tumors	Azacitidine Valproic Acid Carboplatin	-	M.D. Anderson Cancer Center
Azacitidine and Valproic Acid Plus Carboplatin in Patients With Ovarian Cancer	NCT00529022	Solid Tumors	Azacitidine Valproic Acid Carboplatin	-	M.D. Anderson Cancer Center

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Spots Global Cancer Trial Database for depakene

Every month we try and update this database with for depakene cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for depakene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.