VNP40101M and Temozolomide in Treating Patients With Progressive or Relapsed Malignant Glioma

NCT00516282 | Terminated Phase 1 DMC

• 1 other identifier: NU 07C1
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma; adult anaplastic astrocytoma; adult anaplastic oligodendroglioma; adult mixed glioma

Outcome Measures

Primary Outcomes (2)

• 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

• Progression-free survival rate

  To determine the 6 and 12 month progression-free survival rate.

  End of Phase II

Secondary Outcomes (7)

• Toxicities of CLORETAZINE when administered with Temodar®.

  Adverse events are monitored at screening/baseline;day one; termination visit; followup until death.

• MGMT Methylation Status

  Baseline and day seven of every cycle

• Determine overall survival

  All patients will be followed until death

• Response rate to CLORETAZINE after Temodar® in patients with malignant gliomas in first or second relapse

  Day one of every cycle

• Record the toxicities of CLORETAZINE when administered after Temodar

  Continuously after the first dose;within thirty days of each administration of investigational agent

Interventions

CLORETAZINE DRUG

CLORETAZINE will be administered intravenously on day 7. The starting dose of CLORETAZINE will be 100 mg/m2 given within 3 hours after the last dose of Temodar on day 7. CLORETAZINE will be given as an IV infusion over 15-30 minutes via a freely flowing peripheral or central intravenous line. CLORETAZINE will be escalated by 50 mg/m2 for the second cohort then by 25 mg/m2 increments in the following cohorts of 3-6 patients using a standard phase I trial design until a MTD is determined. If dose level 2 has two DLTs then patients will be accrued to a new dose level of 125 mg/m2. Prior to receiving Cloretazine, blood will be drawn for gene methylation studies.

Also known as: VNP40101M

temozolomide DRUG

Temozolomide will be given orally at a dose of 75mg/m2 daily on day 1 through 7. There will be no dose modification for this agent. Prior to receiving Temozolomide, blood will be drawn for gene methylation studies.

Also known as: Temodar

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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:
• 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)

Sponsors & Collaborators

• Northwestern University: lead
• Vion Pharmaceuticals: collaborator

Study Sites (2)

Hematology-Oncology Associates of Illinois

Chicago, Illinois, 60611-2998, United States

Location

Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma; Astrocytoma; Oligodendroglioma; Glioma

Interventions

laromustine; Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jeffrey Raizer, MD

  Northwestern University

  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: August 14, 2007
• First Posted: August 15, 2007
• Study Start: August 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: August 26, 2011

Record last verified: 2011-08

Locations

US (2)