Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Antihypertensive Agents

Vasodilator Agents

Cisplatin

Valproic Acid

Hydralazine

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Neurotransmitter Agents

Hydralazine and magnesium valproate

Punch biopsy of the primary tumor

Alfonso Duenas-Gonzalez, MD, PhD.

The current standard for locally advanced cervical cancer is concurrent cisplatin-based chemotherapy, however, the treatment results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the radiation and chemotherapy effects.

Objective. To determine response rate, safety and biological effects of hydralazine and magnesium valproate when added to cisplatin chemoradiation.

Hypothesis. Hydralazine and magnesium valproate associated to chemoradiation will increase the clinical complete response rate to 95% as compared to 75% as seen in historical controls treated with cisplatin chemoradiation in FIGO stage IIIB patients.

Metodology. A total of 17 FIGO stage IIIB patients with histologically confirmed cervical carcinoma with no previous treatment will be included. Patients will be typed for acetylator status and and then receive either 182 or 83 mg of hydralazine, and magnesium valproate at 40mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy). Clinical response rate, safety and transcriptome changes will be analyzed.

Eligible patients after signing informed consent will undergo study evaluation and then typed for acetylator phenotype before receive either 182 or 83 mg of hydralazine, and magnesium valproate at 30mg/Kg from day -7 to the end of chemoradiation (external and brachytherapy. External beam radiation will be delivered by megavoltage equipment for a dose of 50gy (2Gy fraction from monday to friday) concurrently with cisplatin at 40mg/m2 for six weeks. Within one to two weeks, intracavitary brachytherapy (low-dose rate, Cesium sources) will be delivered to achieve at least 85Gy to point A. A punch biopsy from the primary tumor will be taken at entering the study and at day 8 of hydralazine and valproate treatment (before the first dose of cisplatin and radiation)to assess global gene expression profiling by microarray analysis. Blood samples will be taken to assess global DNA methylation, histone deacetylase activity and plasma levels of hydralazine and valproic acid.

Clinical response and toxicity will be assessed.

Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer

A Phase II Study of Transcriptional Therapy With the DNA Demethylating Hydralazine and the HDAC Inhibitor Valproate Associated to Concomitant Cisplatin Chemoradiation in FIGO Stage III Cervical Cancer.

National Council of Science and Technology, Mexico

Psicofarma S.A. de C.V.

National Institute of Cancerología

Blood and Lymph Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Tab. Valproic acid will be started at a dose of 10 mg per kg per day in two or three divided doses. If well tolerated the dose will be increased to a maximum of 20 mg per kg per day and continued for a period of 3 months. The drug will be continued for another 3 months for a maximum of 6 months in responding patients. The drug will be stopped in all those who develop intolerable side effects or develop disease progression during therapy.

Valproic acid

Vinod Raina, MD, FRCP

Prasanth Ganesan, MD

The purpose of this study is to determine whether Valproic acid, as a single agent is effective in the treatment of Chronic Lymphocytic Leukemia which has relapsed or is refractory to therapy with standard drugs.

Chronic lymphocytic leukemia (CLL) is a disease characterized by a prolonged clinical course. Though various drugs such as alkylating agents, antimetabolites such as fludarabine and targeted antibodies such as rituximab are effective against this condition, relapses are frequent and cure is rare. There exists a subset of CLL patients who are refractory to many of these first line agents. Though one or the other of the above mentioned class of drugs can be substituted for patients who have relapsed or have refractory disease, no therapy has been conclusively proven to have survival advantage in this condition. The costs and toxicities add to the burden of these therapies. Valproic acid is a well studied drug used for the treatment of epilepsy for over 30 years. It has a well documented side effect profile, is generally well tolerated and is inexpensive. Recently, it has been shown to be an inhibitor of the enzyme, Histone de-acetylase(HDAC). Inhibition of HDAC promotes apoptosis, and could lead to the death of CLL cells which harbor defective apoptotic mechanisms. In vitro studies have proven the ability of therapeutic concentrations of Valproic acid to achieve cell kill in cultures of CLL cells. This study aims to identify whether valproic acid, used in standard doses has single agent activity against CLL and to assess its tolerance in these patients.

Study of Efficacy and Safety of Valproic Acid in Chronic Lymphocytic Leukemia (CLL)

Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia

All India Institute of Medical Sciences, New Delhi

Dr. Vinod Raina

Recurrence

Topotecan

Cisplatin + Topotecan plus hydralazine valproate

Placebo

Alfonso Dueñas-Gonzalez, MD PhD

Lucely Cetina, MD

Myrna Candelaria, MD

The current standard for recurrent, persistent or metastatic cervical cancer is palliative chemotherapy with cisplatin topotecan, however, the results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the cytotoxicity of chemotherapy.

Objective. To determine the superiority of epigenetic therapy with hydralazine and valproate plus standard cisplatin topotecan against placebo plus cisplatin topotecan upon progression-free survival.

Hypothesis. Hydralazine and magnesium valproate associated to cisplatin topotecan will increase progression-free survival from 4.6 to 7.6 months as compared with the same regimen of chemotherapy plus placebo.

Randomized, double-blind phase III trial. A total of 143 patients (alpha 0.5, power 0.8)with metastatic, persistent or recurrent cervical cancer without previous systemic treatment will be randomized to cisplatin topotecan + placebo or cisplatin topotecan hydralazine valproate for 6 courses every 3 weeks. Patients will receive an oral dose of hydralazine of 182mg (rapid) or 83mg (slow) according to the acetylator phenotype in a single daily dose and magnesium valproate at an oral dose of 40mg/Kg t.i.d. Both drugs in a slow-release formulation. Experimental drugs or placebo will start from seven days before day 1 of chemotherapy until the end of the sixth course.

Hydralazine Valproate for Cervical Cancer

Randomized, Double-Blind, Phase III Trial of Chemotherapy Plus the Transcriptional Therapy Hydralazine and Magnesium Valproate Versus Chemotherapy Plus Placebo in Recurrent and Metastatic Cervical Cancer.

Lucely Cetina

Lymphoma

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Lymphosarcoma

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Anti-Bacterial Agents

Antibiotics, Antitubercular

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Tubulin Modulators

Antimitotic Agents

Valproate is given in escalating doses to establish maximum tolerable dose when given together with standard treatment in patients with diffuse large B-cell lymphoma; this is the phase I part of the study. When maximum tolerable dose is established, this dose will be given to remaining patients in the phase II part of the study.

Valproate

Vill be given intravenously, 375 mg/m2, every second or third week depending on cycle length (14 or 21 days), for a total of 6 cycles.

Vill be given intravenously, 750 mg/m2, every second or third week depending on cycle length (14 or 21 days) for a total of 6 cycles.

Vill be given intravenously, 50 mg/m2, every second or third week depending on cycle length (14 or 21 days), for a total of 6 cycles.

Vill be given intravenously, 1.2 mg/m2, every second or third week depending on cycle length (14 or 21 days), for a total of 6 cycles.

Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.

Mats Jerkeman, MD, PhD

Patients with previously untreated diffuse large B-cell lymphoma will receive standard treatment with R-CHOP (rituximab,cyclosphosphamide, doxorubicin, vincristine, and prednison) for 6 cycles, cycle length is 14 or 21 days. In addition, valproate is given three times daily day 1-3 in escalated doses. The rationale for adding valproate to standard treatment is invitro data indicating a sensitizing effect to chemotherapy, and an increase in CD 20-expression.

Patients are included in 3+3 cohorts with escalation of valproate dose, planned dos levels are 30, 60, 80, 100, 120, 140 mg/kg/day. A total of 20 patients will be treated at the MTD.

Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma

Valcuria

Lund University Hospital

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

Neoplasms, Glandular and Epithelial

Neuroepithelioma

Etoposide

Etoposide phosphate

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

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

M.D. Anderson Cancer Center

Respiratory Tract (Lung and Bronchial) Diseases

Mesothelioma

Mesothelioma, Malignant

Lung Neoplasms

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Continuous oral administration of valproate plus every 3 weeks, intravenous administration of doxorubicin

Valproate 20-30 mg/kg orally (in order to obtain serum concentration between 50-100 mcg/ml) Doxorubicin 60 mg/m² intravenously every 3 weeks

Valproate plus doxorubicin

Thierry Berghmans, MD

The purpose of this study is to determine the response rate to the combination of doxorubicin and valproate acid in patients with MM failing after at least one previous chemotherapy regimen including platinum derivatives .

Phase II Study of Valproate and Doxorubicin in Malignant Mesothelioma

A Phase II Study Assessing the Activity of Valproate Acid Plus Doxorubicin in Refractory or Recurrent Malignant Mesothelioma

European Lung Cancer Working Party

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer	NCT00404326	Cervical Cancer	Hydralazine and... Punch biopsy of...	18 Years - 70 Years	National Institute of Cancerología
Hydralazine and Valproate Plus Cisplatin Chemoradiation in Cervical Cancer	NCT00404326	Cervical Cancer	Hydralazine and... Punch biopsy of...	18 Years - 70 Years	National Institute of Cancerología
Study of Efficacy and Safety of Valproic Acid in Chronic Lymphocytic Leukemia (CLL)	NCT00810680	Chronic Lymphoc...	Valproic acid	18 Years -	All India Institute of Medical Sciences, New Delhi
Hydralazine Valproate for Cervical Cancer	NCT00532818	Metastatic Cerv...	Hydralazine and... Placebo	18 Years -	National Institute of Cancerología
Study of Efficacy and Safety of Valproic Acid in Chronic Lymphocytic Leukemia (CLL)	NCT00810680	Chronic Lymphoc...	Valproic acid	18 Years -	All India Institute of Medical Sciences, New Delhi
Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma	NCT01622439	Diffuse Large B...	Valproate Rituximab Cyclophosphamid... Doxorubicin Vincristine Prednisone	18 Years - 80 Years	Lund University Hospital
Valproate and Etoposide for Patients With Neuronal Tumors and Brain Metastases	NCT00513162	Neuroectodermal... Brain Metastase... Advanced Cancer	Valproate Etoposide	-	M.D. Anderson Cancer Center
Phase II Study of Valproate and Doxorubicin in Malignant Mesothelioma	NCT00634205	Malignant Mesot...	Valproate plus ...	18 Years -	European Lung Cancer Working Party
Hydralazine Valproate for Cervical Cancer	NCT00532818	Metastatic Cerv...	Hydralazine and... Placebo	18 Years -	National Institute of Cancerología

Spots Global Cancer Trial Database for valproate

Every month we try and update this database with for valproate 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.

Spots Global Cancer Trial Database for valproate

Every month we try and update this database with for valproate 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 valproate 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.