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Azacitidine and Valproic Acid Plus Carboplatin in Patients With Ovarian Cancer
This study is currently recruiting participants.
Verified by M.D. Anderson Cancer Center, December 2008
Sponsors and Collaborators: M.D. Anderson Cancer Center
Celgene Corporation
Information provided by: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00529022
  Purpose

Primary Objectives:

  1. To determine acceptable dosages of valproic acid and carboplatin in a regimen of sequential azacitidine and valproic acid plus carboplatin in the treatment of patients with advanced solid tumor during the phase 1 part.
  2. To assess objective response rates in platinum resistant epithelial ovarian cancer patients treated with sequential azacitidine and valproic acid plus carboplatin during the phase 2 part.
  3. To determine whether DNA methylation, and histone H3 and H4 acetylation of tumor tissue and peripheral blood monocytes are able to predict objective responses.

Secondary Objectives:

  1. To describe toxicity profile.
  2. To assess progression-free survival.
  3. To assess overall survival.

Condition Intervention Phase
Solid Tumors
Drug: Azacitidine
Drug: Valproic Acid
Drug: Carboplatin
Phase I
Phase II

MedlinePlus related topics: Cancer Ovarian Cancer
Drug Information available for: Carboplatin Azacitidine 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/II Trial of Sequential Azacitidine and Valproic Acid Plus Carboplatin in the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer

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

Primary Outcome Measures:
  • To find out if giving azacitidine with valproic acid plus carboplatin can help control advanced cancer. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 65
Study Start Date: August 2007
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Azacitidine + Valproic Acid + Carboplatin
Drug: Azacitidine
75 mg/m^2 Subcutaneous Injection or IV Daily x 5 Days
Drug: Valproic Acid
40 mg/kg PO Daily x 7 days
Drug: Carboplatin
AUC 2 IV Daily Over 60 Minutes

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient has histologically or cytologically confirmed diagnosis of advanced solid tumor (that has progressed following standard therapy or for whom, in the opinion of the investigator, no standard effective therapy is available) during the phase I study. Only patients who have platinum resistant epithelial carcinoma of the ovary, fallopian tube or primary peritoneal carcinoma are enrolled onto the phase II study. According to standard GOG criteria platinum resistant is defined to have had a disease-free interval of shorter than 6 months following platinum treatment.
  2. Patient has measurable or evaluable disease by radiological imaging techniques with documented progression within 1 month before study entry or disease that has not responded to treatment. (Pleural effusions, ascites, osseous metastasis, elevation of tumor marker and lesions located in previously irradiated areas are not considered measurable).
  3. Patient is willing to comply with study procedures to have blood collections for correlative studies.
  4. Patient has an ECOG performance status of 0-2.
  5. Patient must be informed of the investigational nature of this study and must sign and give written IRB approved informed consent in accordance with institutional guidelines.
  6. If patient is of child-bearing potential, she or he has agreed to practice an effective method of birth control during the study and up to 3 months after the last treatment.
  7. Patient has adequate liver and renal function: serum albumin =/>3.0 g/dL; serum bilirubin =/<2.0 mg/dL; ALT=/<3x upper limit of normal (uln); and serum creatinine =/< 2.0 mg/dL or a calculated creatinine clearance of at least 40 ml/min.
  8. Patient has adequate bone marrow reserve. ANC=/>1,500/ul, Platelet count =/>100,000/ul, and Hemoglobin =/>9.0g/dL.

Exclusion Criteria:

  1. Any concurrent chemotherapy.
  2. Underlying medical condition that might be aggravated by treatment or that cannot be controlled, such as active uncontrolled serious infection and cardiac dysfunction.
  3. Medical and psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
  4. Known hypersensitivity to azacitidine, valproic acid, carboplatin or their analogs.
  5. Failure to recover from any prior surgery within 4 weeks of study entry.
  6. Pregnant or lactating.
  7. Any treatment specific for tumor control within 3 weeks of dosing with study drugs (within 2 weeks if given weekly or within 6 weeks for nitrosoureas or mitomycin C) or failure to recover from the toxic effect of any of these therapies prior to study entry. Any investigational drug within 30 days of first day of dosing.
  8. Any signs of intestinal obstruction interfering with nutrition or oral intake.
  9. History of CNS metastasis unless the patient has had surgery or radiation, and does not require oral or intravenous corticosteroids or anticonvulsants.
  10. Advanced malignant hepatic tumors that are defined as the total hepatic metastases more than 25% of hepatic parenchyma.
  11. History of high dose chemotherapy for ovarian cancer in phase II study. High dose chemotherapy is defined as the intensity and/or the density of a chemotherapeutic agent that are beyond standard of care for ovarian cancer treatment.
  12. History of prior malignancy except for adequately treated carcinoma in situ of the uterine cervix, basal cell or squamous cell skin cancer, or other cancer for which the patient has been disease free for at least two years in phase II study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00529022

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
Celgene Corporation
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: 2007-0030
Study First Received: September 11, 2007
Last Updated: December 31, 2008
ClinicalTrials.gov Identifier: NCT00529022  
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancer
Solid Tumors
Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Azacitidine
5-Azacitidine
5-Aza
Vidaza™
5-AZC
AZA-CR
Ladakamycin
NSC-102816
Vidaza
Valproic Acid
Depakene
Carboplatin
Paraplatin

Study placed in the following topic categories:
Ovarian cancer
Ovarian Neoplasms
Gonadal Disorders
Genital Neoplasms, Female
Endocrine System Diseases
Urogenital Neoplasms
Carboplatin
Ovarian Diseases
Ovarian epithelial cancer
Valproic Acid
Fallopian Tube Neoplasms
Genital Diseases, Female
Azacitidine
Fallopian tube cancer
Endocrinopathy
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Neurotransmitter Agents
Antimetabolites, Antineoplastic
Tranquilizing Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Psychotropic Drugs
Central Nervous System Depressants
Enzyme Inhibitors
Antimanic Agents
Pharmacologic Actions
Adnexal Diseases
Neoplasms
Neoplasms by Site
Therapeutic Uses
GABA Agents
Central Nervous System Agents
Anticonvulsants

ClinicalTrials.gov processed this record on January 15, 2009