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

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.