Azacytidine and Valproic Acid in Patients With Advanced Cancers

• Status: Completed
• Trial end date: 2009-10-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: Celgene Corporation
• Treatments: Azacitidine; Histone Deacetylase Inhibitors; Valproic Acid

Criteria

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. No chemotherapy, radiotherapy, investigational agents or surgery within four weeks.

4. ECOG performance status 2 or less.

5. Normal organ and marrow function - ANC > 1500/microL - Platelets > 100,000/microL - Total bilirubin < 2.0 mg/dL - Creatinine < 2.0 mg/dL

6. The effect of azacytidine on the development of human fetus is unknown. Because of the chemotherapy agents are known to be teratogenic, women and men of childbearing potential must agree to use adequate contraception prior to study entry and for the duration of the study.

7. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1. Uncontrolled concurrent illness such as neutropenic fever,shock, symptomatic congestive heart failure (NYHA class III or IV).

2. Hypersensitivity to divalproex sodium, valproic acid, or valproate sodium

3. Known or suspected hypersensitivity to azacitidine or mannitol.

4. Nursing and pregnant women.

5. Patients with urea cycle disorders (UCD): - History of unexplained coma, encephalopathy, or mental retardation - Encephalopathy associated with a protein load

• Pregnancy-related or postpartum encephalopathy - History of elevated plasma ammonia or glutamine - Those with cyclical vomiting and lethargy, episodic extreme irritability, ataxia, low BUN, or protein avoidance. - Those with a family history of UCD or unexplained infant deaths (particularly males).

6. Patients with a known ornithine transcarbamylase disorder, history of unexplained coma or a family history of ornithine transcarbamylase disorder are excluded from this study.

7. Patients younger than 2-year old since valproic acid safety is not proven in this age group.

8. Leukemias and MDS are excluded