Brain and Central Nervous System Tumors Clinical Trial
Official title:
A Phase I/II Trial of Cloretazine® (VNP40101M) and Temodar® (Temozolomide) for Patients With Malignant Glioma in First Relapse or Progression
RATIONALE: Drugs used in chemotherapy, such as temozolomide and VNP40101M, work in different
ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Temozolomide may also stop the growth of tumor cells by blocking blood flow to the
tumor.
PURPOSE: This phase I/II trial is studying the side effects and best dose of VNP40101M when
given together with temozolomide and to see how well it works in treating patients with
progressive or relapsed malignant glioma.
Status | Terminated |
Enrollment | 14 |
Est. completion date | October 2009 |
Est. primary completion date | October 2009 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
DISEASE CHARACTERISTICS: Inclusion criteria: - Histologically proven malignant glioma including any of the following: - Glioblastoma multiforme - Gliosarcoma - Anaplastic astrocytoma - Anaplastic oligodendroglioma - Anaplastic mixed oligoastrocytoma - Malignant astrocytoma not otherwise specified - Unequivocal evidence of tumor recurrence or progression by MRI or CT scan with contrast - No more than one relapse - Patients having undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply: - More than 2 weeks from surgery and have recovered from the effects of surgery - Evaluable or measurable disease following resection of recurrent tumor is not mandated for eligibility into the study if a treatment failure can be evaluated - Enhanced CT scan/ MRI should be done no later than 96 hours in the immediate post-operative period or 4-6 weeks post-operatively - If the 96-hour scan is more than 2 weeks from registration, the scan needs to be repeated - A baseline scan should be performed within 14 days prior to registration and on a steroid dosage that has been stable for 5 or more days otherwise a new baseline MRI/CT is required - The same type of scan (i.e., MRI or CT scan) must be used throughout the period of protocol treatment for tumor measurement - Must have failed prior external-beam radiotherapy - Must have failed one prior systemic treatment with chemotherapy or biologic agents PATIENT CHARACTERISTICS: Inclusion criteria: - Karnofsky performance status 60-100% - Life expectancy > 12 weeks - WBC > 3,000/mm³ - ANC > 1,500/mm³ - Platelet count > 100,000/mm³ - Hemoglobin > 10 mg/dL - AST and ALT < 4 times upper limit of normal (ULN) - Bilirubin < 2 times ULN - Creatinine < 1.5 times ULN - Fertile patients must use acceptable contraceptive methods (abstinence, intrauterine device [IUD], oral contraceptive or double barrier device) - Negative pregnancy test - Not pregnant or nursing Exclusion criteria: - Active uncontrolled bleeding - Active infection of any kind - Unwilling or unable to follow protocol requirements or to give informed consent - Active heart disease including any of the following: - Myocardial infarction within the past 3 months - Uncontrolled arrhythmias - Uncontrolled coronary artery disease - Uncontrolled congestive heart failure - Known HIV-positive patients (HIV testing is not required) - History of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless in complete remission and off all therapy for that disease for a minimum of 3 years PRIOR CONCURRENT THERAPY: Inclusion criteria: - See Disease Characteristics - Recovered from prior therapy - At least 2 weeks since prior vincristine - More than 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas) - More than 4 weeks since prior radiotherapy - More than 4 weeks since prior experimental biologic agents (e.g., EGFR inhibitors, etc) - More than 3 weeks since prior procarbazine administration - More than 2 weeks since prior non-cytotoxic agents (e.g., interferon, tamoxifen, thalidomide, or isotretinoin) - Radiosensitizer does not count - At least 2 weeks since prior and no concurrent enzyme inducing anticonvulsants - If patient is on an enzyme inducing anticonvulsant, they may be converted to a non-enzyme inducing anticonvulsant Exclusion criteria: - Any other concurrent standard or investigational treatment for cancer, or any other investigational agent for any indication - Concurrent disulfiram |
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Hematology-Oncology Associates of Illinois | Chicago | Illinois |
United States | Northwestern University | Chicago | Illinois |
Lead Sponsor | Collaborator |
---|---|
Northwestern University | Vion Pharmaceuticals |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | MTD of CLORETAZINE | To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse | At the end of phase one | Yes |
Primary | Progression-free survival rate | To determine the 6 and 12 month progression-free survival rate. | End of Phase II | No |
Secondary | Toxicities of CLORETAZINE when administered with Temodar®. | To record the toxicities of CLORETAZINE when administered with Temodar®. (Toxicity is assessed continuously through routine medical monitoring of the patient throughout each cycle and all adverse events are recorded cumulatively on the case report forms). |
Adverse events are monitored at screening/baseline;day one; termination visit; followup until death. | Yes |
Secondary | MGMT Methylation Status | To determine MGMT methylation status as well as other methylation patterns in blood correlate with outcome. | Baseline and day seven of every cycle | No |
Secondary | Determine overall survival | To determine overall survival. | All patients will be followed until death | No |
Secondary | Response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse | To determine the response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse. | Day one of every cycle | No |
Secondary | Record the toxicities of CLORETAZINE when administered after Temodar | To record the toxicities of CLORETAZINE when administered after Temodar® | Continuously after the first dose;within thirty days of each administration of investigational agent | Yes |
Secondary | Measure the level of AGT expression | To measure the level of AGT expression in peripheral blood monocytes before treatment with Temodar® and just prior to the administration of CLORETAZINE. | Day seven of every cycle | Yes |
Secondary | CSF penetration of CLORETAZINE | To determine CSF penetration of CLORETAZINE once the MTD is reached from phase I and correlate with serum/plasma PK | Day seven of cycle one of Phase 2 only | Yes |
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