Valproic Acid and Bevacizumab in Patients With Advanced Cancer - Full Text View

Sponsored by:	M.D. Anderson Cancer Center
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00530907

Purpose

Primary Objective:

To determine safety, tolerance of side effects, and the maximally tolerated dose of the combination of valproic acid and bevacizumab in patients with advanced cancer.

Secondary Objectives:

To assess the in vivo biological effects of this combination. These will include analysis of angiogenesis surrogate markers and histone modifications on peripheral blood mononuclear cells.
To assess the clinical efficacy of this combination in patients with advanced cancer by describing objective responses by standard criteria.

Condition	Intervention	Phase
Advanced Cancer	Drug: Valproic Acid Drug: Bevacizumab	Phase I

MedlinePlus related topics: Cancer

Drug Information available for: Bevacizumab Divalproex sodium Valproate Sodium Valproic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase I Study of Valproic Acid Given in Combination With Bevacizumab in Patients With Advanced Cancer to Determine Safety and Tolerability

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

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. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	48
Study Start Date:	June 2007
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Valproic Acid + Bevacizumab	Drug: Valproic Acid 10 mg/kg PO daily x 28 days Drug: Bevacizumab 2.5 mg/kg IV over 90 minutes every 2 weeks

Detailed Description:

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.

Before you can start receiving the study drugs, you will have screening tests. These tests will help the study doctor decide if you are eligible to take part in this study.

You will be asked questions about your medical history.
You will have a complete physical exam, including measurement of your vital signs (blood pressure, breathing rate, and heart rate), height, and weight.
You will have a neurological evaluation to check the function of your brain and spinal cord. For this exam, you will be asked several questions about any changes you have noticed in your vision and hearing, and your muscle strength, how you respond to touch, and how you walk will be checked.
Blood (about 2 tablespoons) and urine samples will be collected for routine tests.
Women who are able to have children must have a negative urine pregnancy test.
You will also have either a computed tomography (CT) or magnetic resonance imaging (MRI) scan of the tumor.

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 (a capsule) each day for 28 days. 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. 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.
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 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 48 patients will take part in this study. All will be enrolled at M. D. Anderson.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with pathologically confirmed malignancy that is metastatic or unresectable and refractory to standard therapy, or for whom there is no standard therapy that induces complete remission (CR) of at least 10% or an increased survival of at least 3 months.
There is no maximum allowable number of prior chemotherapy regimens, provided all other eligibility criteria are met.
ECOG performance status less than 2.
Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count greater than or equal to 1,000/mcL
- platelets greater than 50,000/mcL
- total bilirubin less than 2 mg/dl
- creatinine less than 2 mg/dl
The effects of bevacizumab on the developing human fetus are unknown. For this reason and because valproic acid is known to be teratogenic, women of child-bearing potential and men who may impregnate a woman must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
Ability to understand and the willingness to sign an MD Anderson IRB approved written informed consent document.
Both men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

Patients who have had chemotherapy or radiotherapy within 4 weeks prior to receiving first dose of study drug or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
Patients may not be receiving any other investigational agents for 28 days prior to first dose of drug on this study, and while patient(pt) is receiving this study drug.
Patients whose brain mets or primary brain tumor includes symptoms that in the opinion of the principle investigator would either put the patients at unacceptable risk greater than the risk of the underlying cancer, or if the treatment would unacceptably confound the analysis of the toxicity assessment.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or valproic acid.
Major surgery within the previous four weeks.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, HTN (with 2 or more antihypertensives), unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
Pregnant women are excluded from this study because valproic acid is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with valproic acid and bevacizumab, breastfeeding should be discontinued if the mother is treated with these agents.
Patients who are already on antiepileptic agents, for example; phenytoin, valproic acid, and neurontin will be excluded.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00530907

Contacts

Contact: Siqing Fu, MD, PhD

713-792-9669

Locations

United States, Texas
U.T. M.D. Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Siqing Fu, MD, PhD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Investigators

Principal Investigator:

Siqing Fu, MD, PhD

U.T.M.D. Anderson Cancer Center

More Information

The University of Texas M.D.Anderson Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	U.T. M.D. Anderson Cancer Center ( Siqing Fu, MD, PhD/Assistant Professor )
Study ID Numbers:	2005-0676
Study First Received:	September 14, 2007
Last Updated:	December 12, 2008
ClinicalTrials.gov Identifier:	NCT00530907
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Advanced Cancer
Valproic Acid
Bevacizumab
Avastin

Study placed in the following topic categories:

Bevacizumab
Valproic Acid

Additional relevant MeSH terms:

Neurotransmitter Agents
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents

Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Therapeutic Uses
GABA Agents
Growth Inhibitors
Angiogenesis Modulating Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 16, 2009