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

NCT00629343 | Completed Phase 1 Results DMC

• 1 other identifier: AAAC3255
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Soft Tissue Sarcoma; Mesothelioma

Keywords

Soft Tissue Sarcoma; Mesothelioma; Azacitidine; Temozolomide; Temodar

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Temozolomide

  Maximum tolerated dose of temozolomide when used in combination with azacitidine

  Up to 26 weeks for each dosing cohort

• Maximum Tolerated Dose of Azacitidine

  Maximum tolerated dose of azacitidine when used in combination with temozolomide

  Up to 26 weeks for each dosing cohort

Study Arms (1)

Treatment

EXPERIMENTAL

Subjects will receive azacitidine in combination with temozolomide

Drug: Azacitidine; Drug: Temozolomide

Interventions

Azacitidine DRUG

Azacitidine will be delivered sub-cutaneously for 5 days

Also known as: Vidaza

Treatment

Temozolomide DRUG

Temozolomide will be given starting on day 8 for 5 days at a dose of 200 mg/m2 po qd x 5 days

Also known as: Temodar

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Columbia University: lead
• Schering-Plough: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Sarcoma; Mesothelioma

Interventions

Azacitidine; Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Dacarbazine; Triazenes; Imidazoles; Azoles

Results Point of Contact

• Title: Robert Taub, MD, PhD
• Organization: Columbia University

rnt1@columbia.edu

(212) 305-4076

Study Officials

• Robert N Taub, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2008
• First Posted: March 6, 2008
• Study Start: October 1, 2007
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: June 5, 2025
• Results First Posted: June 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)