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

Phase 1
Open (Enrolling)
Advanced Cancer

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Trial Information

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

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

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.

Inclusion Criteria:

1. 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.

2. There is no maximum allowable number of prior chemotherapy regimens, provided all
other eligibility criteria are met.

3. ECOG performance status less than 2.

4. 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

5. 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.

6. Ability to understand and the willingness to sign an MD Anderson IRB approved written
informed consent document.

7. Both men and women of all races and ethnic groups are eligible for this trial.

Exclusion Criteria:

1. 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 have received palliative
radiation immediately before (or during) treatment provided radiation is not to the
only target lesion available.

2. Patients may not be receiving any other investigational agents for 28 days prior to
first dose of drug on this study, and while pt is receiving this study drug.

3. 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.

4. History of allergic reactions attributed to compounds of similar chemical or biologic
composition to bevacizumab or valproic acid .

5. Major surgery within the previous four weeks.

6. 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.

7. 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.

8. Patient who are already on antiepileptic agents, for example; phenytoin, valproic
acid, and neurontin will be excluded.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Highest tolerable dose of bevacizumab in combination with valproic acid

Outcome Time Frame:

28 day cycle

Safety Issue:


Principal Investigator

Jennifer Wheler, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2007

Completion Date:

Related Keywords:

  • Advanced Cancer
  • Advanced Cancer
  • Valproic Acid
  • Depakene
  • Bevacizumab
  • Avastin
  • Anti-VEGF monoclonal antibody
  • rhuMAb-VEGF
  • Neoplasms



UT MD Anderson Cancer Center Houston, Texas  77030