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

Primary Purpose

Central Nervous System Neoplasms, Neoplasm Metastasis

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Temozolomide

About this trial

This is an interventional treatment trial for Central Nervous System Neoplasms focused on measuring Lung Neoplasm, Breast Neoplasm, Melanoma, Central Nervous System Neoplasms, Neoplasm Metastasis, Neoplasm Second Primary, Peripheral Blood Stem Cell Transplantation

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Tufts Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT00629187

First Posted

February 25, 2008

Last Updated

April 26, 2012

Sponsor

Tufts Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00629187

Brief Title

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

Acronym

CN-306

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

2. Study Status

Record Verification Date

April 2012

Overall Recruitment Status

Terminated

Why Stopped

The study was stopped due to lack of adequate enrollment.

Study Start Date

April 2004 (undefined)

Primary Completion Date

April 2012 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tufts Medical Center

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

Temodar

Intervention Description

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).

Primary Outcome Measure Information:

Title

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

Time Frame

5 years

Secondary Outcome Measure Information:

Title

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

Time Frame

5 years

Title

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

Time Frame

5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andreas Klein, MD

Organizational Affiliation

Tufts Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tufts Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02111

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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