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

NCT00629187 | Terminated Phase 1

• 1 other identifier: CN-306
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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. This study is only available at Tufts Medical Center.

Conditions

Central Nervous System Neoplasms; Neoplasm Metastasis

Keywords

Lung Neoplasm; Breast Neoplasm; Melanoma; Central Nervous System Neoplasms; Neoplasm Metastasis; Neoplasm Second Primary; Peripheral Blood Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Determine the maximum tolerated dose of temozolomide with hematopoietic stem cell rescue in patients with recurrent CNS malignancy

  5 years

Secondary Outcomes (2)

• Estimate the response rate, response duration and survival according to established response definitions

  5 years

• Determine the pharmacokinetics of high daily dosing of temozolomide in the transplant setting

  5 years

Study Arms (1)

1

EXPERIMENTAL

Drug: Temozolomide

Interventions

Temozolomide DRUG

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).

Also known as: Temodar

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tufts Medical Center: lead

Study Sites (1)

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Neoplasm Metastasis; Lung Neoplasms; Breast Neoplasms; Melanoma; Neoplasms, Second Primary

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Andreas Klein, MD

  Tufts Medical Center

  PRINCIPAL INVESTIGATOR

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 25, 2008
• First Posted: March 5, 2008
• Study Start: April 1, 2004
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: April 27, 2012

Record last verified: 2012-04

Locations

US (1)