Clinical trial NCT00629187: Safety Study of High Dose Temozolomide to Treat Relapsed/Refractory Central Nervous System (CNS) Malignancy
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
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
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2008-03-05
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 Medical Center.

Eligibility 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.

Primary outcomes:
measure: Determine the maximum tolerated dose of temozolomide with hematopoietic stem cell rescue in patients with recurrent CNS malignancy
timeFrame: 5 years
Secondary outcomes:
measure: Estimate the response rate, response duration and survival according to established response definitions
timeFrame: 5 years
measure: Determine the pharmacokinetics of high daily dosing of temozolomide in the transplant setting
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Andreas Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: