Safety Study of High Dose Temozolomide to Treat Relapsed/Refractory Central Nervous System (CNS) Malignancy (CN-306)

Phase I Dose Escalation Study of Temozolomide With Autologous Stem Cell Rescue for Patients With Relapsed/Refractory CNS Malignancy Including Isolated Metastatic Disease

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.

Study Overview

• Status: Terminated
• Conditions: Neoplasm Metastasis; Central Nervous System Neoplasms
• Intervention / Treatment: Drug: Temozolomide

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.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: 1

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).; Other Names: Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the maximum tolerated dose of temozolomide with hematopoietic stem cell rescue in patients with recurrent CNS malignancy	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Tufts Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (ACTUAL): April 1, 2012
• Study Completion (ACTUAL): April 1, 2012

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: February 26, 2008
• First Posted (ESTIMATE): March 5, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 27, 2012
• Last Update Submitted That Met QC Criteria: April 26, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: Melanoma; Breast Neoplasm; Peripheral Blood Stem Cell Transplantation; Lung Neoplasm; Neoplasm Metastasis; Central Nervous System Neoplasms; Neoplasm Second Primary
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neoplasms by Site; Neoplastic Processes; Neoplasms; Neoplasm Metastasis; Nervous System Neoplasms; Central Nervous System Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: CN-306