Phase I Dose-Escalation Study Of Azacitidine In Combination With Temozolomide

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00629343
Recruitment Status : Unknown
Verified November 2012 by Columbia University.
Recruitment status was:  Active, not recruiting
First Posted : March 6, 2008
Last Update Posted : November 8, 2012
Celgene Corporation
Information provided by (Responsible Party):
Columbia University

Brief Summary:
The purpose of this study is to determine safety and toxicity for the combination of Temozolomide and Azacitidine in the treatment of Advanced Soft Tissue Sarcoma or Malignant Mesothelioma. This is a single-center, open-label, single-arm Phase I dose-escalation trial. Patients will be evaluated with complete history and physical as well as laboratory studies (complete blood count, metabolic panel, liver function tests), biopsy, and imaging of all sites of measurable disease. This study will be conducted over the course of 3 years.

Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Mesothelioma Drug: Azacitidine In Combination With Temozolomide Phase 1

Detailed Description:

The primary objective of the study is to determine the clinical and laboratory toxicities as well as acceptability/tolerance of this dose schedule of combined drug treatment with temozolomide and azacitidine.

Secondary objectives include determination of biochemical response to azacitidine as defined as change in methylation status. We will specifically be looking at changes in genome wide methylation patterns as determined by two high-throughput platforms:

  1. A single nucleotide polymorphism chip-based method (MSNP) for genome wide epigenetic profiling
  2. CpG island promoter arrays will be performed to focus on promoter methylation status.

We will also monitor clinical response, time to progression and overall survival.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose-Escalation Study Of Azacitidine In Combination With Temozolomide In Patients With Unresectable Or Metastatic Soft Tissue Sarcoma or Malignant Mesothelioma
Study Start Date : October 2007
Actual Primary Completion Date : October 2012
Estimated Study Completion Date : August 2014

Arm Intervention/treatment
Experimental: Treatment Drug: Azacitidine In Combination With Temozolomide
mg, oral

Primary Outcome Measures :
  1. The primary endpoint is dose limiting toxicity. [ Time Frame: Study Completion ]

Secondary Outcome Measures :
  1. Clinical response, time to progression and overall survival. [ Time Frame: Study Completion ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically confirmed soft tissue sarcoma or mesothelioma.
  • Ineligible for other high priority national or institutional study.
  • Non-pregnant, non-lactating.
  • Recurrent or progressive disease defined as an increase in size of any existing tumor mass, or the development of new tumor mass or masses, which is not amenable to definitive surgical therapy.
  • Measurable disease defined as lesions that can be measured in at least one dimension by physical examination or by means of medical imaging techniques. Ascites and pleural effusions will not be considered measurable disease.
  • Prior chemotherapy is allowed with the exception of prior treatment with Temozolomide or Azacitidine. Patients must have received prior 1st line therapy. There is no upper limit to the number of prior therapies received. Prior treatment with an alkylating agent is acceptable.
  • Prior radiation therapy is allowed.
  • At least 4 weeks since prior chemotherapy or at least 6 weeks since prior radiation therapy.
  • Patients may have had another cancer but there must be convincing clinical evidence that the sarcoma is the disease requiring therapeutic intervention. (i.e. Several sarcoma patients have had had a prior cancer [Hodgkin's disease or breast cancer] treated years previously and then developed a clinically active sarcoma.)
  • Clinical parameters: Life expectancy > 3 months, Age > 18 years, Performance Karnofsky performance status of greater than or equal to 60%.
  • Required initial laboratory data:

    • Absolute neutrophil count > 1,500/mm3
    • Hemoglobin > 10.0 g/dl
    • Platelet count > 100,000/mm3
    • Total Bilirubin < 1.5 times upper limit of normal (ULN) for the laboratory.
    • Transaminases: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels must be < 2 x ULN. If there is known hepatic metastasis, transaminases may be < 5 times upper limit of normal.
    • Serum creatinine levels < 1.5 x ULN.
    • Women of child-bearing potential must have a negative serum pregnancy test prior to initiation of treatment.
  • Men and women of child-bearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter (approximately 3 months).
  • Capable of providing written, informed consent. Each patient must be completely aware of the nature of his/her disease process and must willingly give consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks and discomforts.
  • No serious medical or psychiatric illness preventing informed consent or intensive treatment (e.g. serious infection).
  • No uncontrolled central nervous system metastases.

Exclusion Criteria:

  • Known or suspected hypersensitivity to azacitidine or mannitol
  • Pregnant or breast-feeding
  • Histology other than soft-tissue sarcoma or mesothelioma
  • Active or uncontrolled infection or other serious systemic disease
  • Prior treatment with temozolomide or azacitidine
  • Pregnant or lactating women
  • Uncontrolled central nervous system metastases
  • Liver metastases
  • Patients will not be excluded if they do not wish to participate in the second biopsy for tissue evaluation
  • Subjects who have not had prior chemotherapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00629343

United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Celgene Corporation
Principal Investigator: Robert N Taub, MD Columbia University

Responsible Party: Columbia University Identifier: NCT00629343     History of Changes
Other Study ID Numbers: AAAC3255
First Posted: March 6, 2008    Key Record Dates
Last Update Posted: November 8, 2012
Last Verified: November 2012

Keywords provided by Columbia University:
Soft Tissue Sarcoma

Additional relevant MeSH terms:
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Mesothelial
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antimetabolites, Antineoplastic
Enzyme Inhibitors