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Brain and Central Nervous System TumorsPhase 1NCT00516282

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

A Phase 1 study testing CLORETAZINE and temozolomide in people with Brain and Central Nervous System Tumors, run by Northwestern University at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Brain and Central Nervous System Tumors
What is being tested?
CLORETAZINE and temozolomide
How many people
14 participants
Where
2 sitesUnited States
Study dates
Aug 2007to Oct 2009
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically proven malignant glioma including any of the following:
  • Glioblastoma multiforme
  • Gliosarcoma
  • Anaplastic astrocytoma
  • Anaplastic oligodendroglioma
  • Anaplastic mixed oligoastrocytoma
Show all 42Show fewer
  • 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:
  • 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
  • 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

Who cannot join

  • 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
Show all 13Show fewer
  • 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:
  • Any other concurrent standard or investigational treatment for cancer, or any other investigational agent for any indication
  • Concurrent disulfiram

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Hematology-Oncology Associates of Illinois

    Chicago, Illinois, 60611-2998

  • Northwestern University

    Chicago, Illinois, 60611-3013

Other trials in United States

About this study

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.

Read the detailed description

OBJECTIVES:

  • To determine the maximum tolerated dose (MTD) of VNP40101M when administered with temozolomide in patients with progressive or relapsed (first relapse) malignant glioma. (Phase I)
  • To record the toxicities of VNP40101M when administered with temozolomide. (Phase I and II)
  • To measure the level of AGT expression in peripheral blood monocytes before treatment with temozolomide and just prior to the administration of VNP40101M. (Phase I and II)
  • To determine MGMT methylation status as well as other methylation patterns in blood and tissue from patients treated with this regimen and correlate with outcome. (Phase I and II)
  • To determine the 6- and 12-month progression-free survival rates of patients treated with this regimen. (Phase II)
  • To determine overall survival of patients treated with this regimen. (Phase II)
  • To determine the complete and partial response rates in patients treated with this regimen. (Phase II)
  • To determine CSF penetration of VNP40101M once the MTD is reached from phase I and correlate with serum/plasma pharmacokinetics. (Phase II)

OUTLINE:

  • Phase I: Patients receive oral temozolomide on days 1-7 and VNP40101M IV over 15-30 minutes 2 hours after the last dose of temozolomide on day 7. Treatment repeats every 7 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of VNP40101M until the maximum tolerated dose (MTD) is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicity.

  • Phase II: Patients receive oral temozolomide and VNP40101M as in phase I. VNP40101M is given at the MTD determined in phase I.

In both phases, patients complete the Functional Assessment of Cancer Therapy-Brain (FACT-BR) questionnaire on day 1 of each course.

Blood is collected for in vitro isolation of mononuclear cells for analysis of O^6 alkylguanine DNA alkyltransferase on days 1 and 7 of course 1. Blood, plasma, CSF, and formalin-fixed paraffin-embedded tissue blocks are collected for gene methylation studies, including MGMT, at baseline and on day 1 of each course.

Being tested
CLORETAZINE, temozolomide
Keywords
adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma
Medical subject headings
Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Astrocytoma, Oligodendroglioma, Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CLORETAZINEDrug

    Also called VNP40101M

    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.

  • temozolomideDrug

    Also called Temodar

    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.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. MTD of CLORETAZINE

    To determine the MTD of CLORETAZINE when administered with Temodar® in patients with malignant gliomas in first or second relapse

    Measured: At the end of phase one

  2. Progression-free survival rate

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

    Measured: End of Phase II

Secondary outcomes (7)

  1. 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).

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

  2. MGMT Methylation Status

    To determine MGMT methylation status as well as other methylation patterns in blood correlate with outcome.

    Measured: Baseline and day seven of every cycle

  3. Determine overall survival

    To determine overall survival.

    Measured: All patients will be followed until death

  4. 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.

    Measured: Day one of every cycle

  5. Record the toxicities of CLORETAZINE when administered after Temodar

    To record the toxicities of CLORETAZINE when administered after Temodar®

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

  6. 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.

    Measured: Day seven of every cycle

  7. CSF penetration of CLORETAZINE

    To determine CSF penetration of CLORETAZINE once the MTD is reached from phase I and correlate with serum/plasma PK

    Measured: Day seven of cycle one of Phase 2 only

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionOct 2009
  4. Study completionOct 2009

Why it stopped: The pharmaceutical collaborator filed for bankruptcy and as a result, the study was unable to move into the phase II portion.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00516282
Sponsor's protocol ID
NU 07C1
Status last verified
Aug 2011
First submitted
14 Aug 2007
Last updated
26 Aug 2011
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CLORETAZINE and temozolomide in people with Brain and Central Nervous System Tumors, run by Northwestern University at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 26 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The pharmaceutical collaborator filed for bankruptcy and as a result, the study was unable to move into the phase II portion.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MTD of CLORETAZINE (time frame: At the end of phase one). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00516282.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2011.

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