Safety Study of High Dose Temozolomide to Treat Relapsed/Refractory Central Nervous System (CNS) Malignancy - Full Text View

Sponsors and Collaborators:	Tufts Medical Center Schering-Plough
Information provided by:	Tufts Medical Center
ClinicalTrials.gov Identifier:	NCT00629187

Purpose

The goal of this study is to find the maximum dose of a drug, temozolomide, that can safely be given to subjects with brain tumors. Past studies showed that the maximum dose of temozolomide was limited by low blood counts. The investigators will use blood stem cells collected from bone marrow to help subjects recover their blood counts, a procedure called autologous stem cell transplant or stem cell rescue. This way, the investigators expect to be able to safely deliver very high doses of temozolomide.

Condition	Intervention	Phase
Central Nervous System Neoplasms Neoplasm Metastasis	Drug: Temozolomide	Phase I

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Pharmacokinetics Study
Official Title:	Phase I Dose Escalation Study of Temozolomide With Autologous Stem Cell Rescue for Patients With Relapsed/Refractory CNS Malignancy Including Isolated Metastatic Disease

Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:

Determine the maximum tolerated dose of temozolomide with hematopoietic stem cell rescue in patients with recurrent CNS malignancy [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Estimate the response rate, response duration and survival according to established response definitions [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Determine the pharmacokinetics of high daily dosing of temozolomide in the transplant setting [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	25
Study Start Date:	April 2004
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: Temozolomide Before taking part in this study, subjects will have stem cells collected in a procedure called apheresis. Once on this study, subjects will be admitted to the hospital and receive daily doses of temozolomide by mouth for 5 days. Stem cells will be given back to subjects who will remain in the hospital until blood counts have recovered. Doses of temozolomide will range from 350 mg to 1500 mg/m(squared) daily for 5 days (total dose 1750 to 7500 mg/m(squared).

Arms

Assigned Interventions

1: Experimental

Drug: Temozolomide

Before taking part in this study, subjects will have stem cells collected in a procedure called apheresis. Once on this study, subjects will be admitted to the hospital and receive daily doses of temozolomide by mouth for 5 days. Stem cells will be given back to subjects who will remain in the hospital until blood counts have recovered. Doses of temozolomide will range from 350 mg to 1500 mg/m(squared) daily for 5 days (total dose 1750 to 7500 mg/m(squared).

Detailed Description:

High dose chemotherapy and autologous stem cell transplant is an accepted treatment alternative for patients with brain tumors. Temozolomide has been approved for use by the United States Food and Drug Administration (FDA) for certain tumors of the brain. The doses of temozolomide given in this study will be higher than approved by the FDA and higher than those given in any prior studies.

Over 25 subjects will be enrolled on this study over a period of 5 years. This study will only be available at Tufts-New England Medical Center.

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients or their health care proxies must be able to provide consent to participate in this trial.
Patients must have one of the following diagnoses which has not responded or recurred following at least one prior chemotherapy regimen or radiation therapy:
- anaplastic astrocytoma, glioblastoma multiforme or oligodendroglioma
- primary CNS lymphoma
- malignant disease metastatic to the CNS
Patients must be candidates for high dose chemotherapy and autologous stem cell transplant according to the following criteria:
- Patients must be between the ages of 18 and 70 years (inclusive)
- Patients must have a left ventricular ejection fraction greater than or equal to 45% by MUGA or echocardiogram
- Patients must have adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50% of predicted
- Patients must have serum direct bilirubin less than or equal to 2.0 mg/dl and transaminases less than or equal to 3x institutional upper limit of normal
- Patients must have serum creatinine less than or equal to 2 mg/dl with creatinine clearance greater than or equal to 60 ml/min (either calculated or measured)
- Patients must have an ECOG performance status between 0 and 2
Patients must be at least 4 weeks from last cytoreductive chemotherapy.
Expected survival of at least 3 months

Exclusion Criteria:

Patients with uncontrolled metastatic disease outside of the CNS which would itself, in the investigator's opinion, limit survival to less than 6 months
Patients with uncontrolled seizures are ineligible.
Patients with a history of myocardial infarction within the preceding 6 months, significant arrhythmia within the preceding 3 months, or uncontrolled hypertension or congestive heart failure are ineligible.
Patients with unstable angina are ineligible.
Pregnant or lactating women are ineligible.
Male and female patients who do not agree to practice approved methods of birth control for the duration of the study are ineligible.
Patients with uncontrolled, active infection are ineligible.
Patients infected with HIV are ineligible.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00629187

Contacts

Contact: Andreas Klein, MD	(617) 636-2520 ext 6-2520	aklein2@tufts-nemc.org
Contact: Carrie Grodman, RN	617.636.2682 ext 6-2682	cgrodman@tufts-nemc.org

Locations

United States, Massachusetts
Tufts-New England Medical Center	Recruiting
Boston, Massachusetts, United States, 02111
Contact: Andreas Klein, MD 617-636-2520 ext 6-2520 aklein2@tufts-nemc.org
Contact: Carrie Grodman, RN 617.636.2682 ext 6-2682 cgrodman@tufts-nemc.org
Principal Investigator: Andreas Klein, MD

Sponsors and Collaborators

Tufts Medical Center

Schering-Plough

Investigators

Principal Investigator:

Andreas Klein, MD

Tufts Medical Center

More Information

Tufts-NEMC Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	Tufts-New England Medical Center ( Andreas Klein, MD, Assistant Professor of Medicine )
Study ID Numbers:	CN-306
Study First Received:	February 25, 2008
Last Updated:	April 8, 2008
ClinicalTrials.gov Identifier:	NCT00629187
Health Authority:	United States: Institutional Review Board

Keywords provided by Tufts Medical Center:

Lung Neoplasm
Breast Neoplasm
Melanoma
Central Nervous System Neoplasms

Neoplasm Metastasis
Neoplasm Second Primary
Peripheral Blood Stem Cell Transplantation

Study placed in the following topic categories:

Lung Neoplasms
Neoplasm Metastasis
Breast Neoplasms
Central Nervous System Neoplasms

Temozolomide
Nervous System Neoplasms
Melanoma

Additional relevant MeSH terms:

Neoplastic Processes
Neoplasms
Neoplasms by Site
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009