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Brain and Central Nervous System TumorsPhase 1NCT00544284

Bortezomib and Temozolomide in Treating Patients With Brain Tumors or Other Solid Tumors That Have Not Responded to Treatment

A Phase 1 study testing bortezomib, temozolomide and pharmacological study in people with Brain and Central Nervous System Tumors and Lymphoma, run by City of Hope Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
bortezomib, temozolomide and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
Jan 2005to Jan 2012
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

  • Karnofsky performance status 60-100%
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 2.0 mg/dL
  • AST ≤ 4.0 x ULN
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  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patient must be able to understand and is willing to sign a written informed consent document
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosourea-containing chemotherapy), immunotherapy, or radiotherapy and recovered
  • More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes for patients in group A
  • Recovered from major surgery
  • Corticosteroids for cerebral edema allowed provided the patient is on a stable dose for at least 1 week

Who cannot join

  • Any of the following conditions:
  • Myocardial infarction within the past 6 months or New York Heart Association class III or IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • ECG evidence of acute ischemia or active conduction system abnormalities
  • Any ECG abnormalities prior to study entry must be documented by the investigator as not medically relevant
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  • Serious medical or psychiatric illness that would, in the opinion of the investigator, potentially interfere with the completion of treatment
  • History of sensitivity to boron or mannitol
  • PRIOR CONCURRENT THERAPY:
  • Patients enrolled on another clinical trial
  • HIV-positive patients on antiretroviral therapy
  • Concurrent chemotherapy or radiotherapy
  • Patient requires anti-seizure medication but is not on a stable dose and agent of anti-seizure medication

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010-3000

  • City of Hope Medical Group

    Pasadena, California, 91105

Other trials in United States

About this study

Official title: A Phase I Study of Bortezomib and Temozolomide in Patients With Refractory Solid Tumors

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of bortezomib when given together with temozolomide in treating patients with brain tumors or other solid tumors that have not responded to treatment.

Read the detailed description

OBJECTIVES:

Primary

  • To determine the dose-limiting toxicities and maximum tolerated doses of bortezomib and temozolomide in patients with recurrent high-grade gliomas, recurrent metastatic brain tumors, or other refractory solid tumors.

Secondary

  • To evaluate the pharmacokinetics of bortezomib in patients taking hepatic enzyme-inducing anticonvulsants (Group A) and in those who are not (Group B).
  • To describe the proportion of study patients treated with bortezomib and temozolomide who obtain a confirmed complete response or partial response.
  • To report the percentage of patients with 6-month progression-free survival.

OUTLINE: Patients are stratified according to concurrent hepatic enzyme-inducing anticonvulsants (HEIAs) (Group A) versus concurrent anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drugs (Group B).

  • Group A: Patients receive oral temozolomide once a day on days 1-5 and bortezomib IV on days 2, 5, 9, and 12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Group B: Patients receive temozolomide and bortezomib as in group A. Cohorts of patients in both groups receive escalating doses of both study drugs until the maximum tolerated doses are determined.

All patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for bortezomib concentration (groups A and B) and trough levels of anticonvulsants (group A only).

Keywords
adult glioblastoma, adult anaplastic astrocytoma, adult giant cell glioblastoma, recurrent adult brain tumor, adult gliosarcoma, adult mixed glioma, adult anaplastic oligodendroglioma, primary central nervous system lymphoma, adult diffuse astrocytoma, adult brain stem glioma, adult central nervous system germ cell tumor, adult choroid plexus tumor, adult craniopharyngioma, adult ependymoblastoma, adult medulloblastoma, adult supratentorial primitive neuroectodermal tumor (PNET), adult anaplastic ependymoma, adult ependymoma, adult myxopapillary ependymoma, adult subependymoma
Medical subject headings
Central Nervous System Neoplasms, Lymphoma, Neoplasm Metastasis, Glioblastoma, Astrocytoma, Brain Neoplasms, Gliosarcoma, Glioma

What participants receive

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

Study groups in NCT00544284
Study groupRoleWhat they receive
Treatment (temozolomide, bortezomib)ExperimentalGROUP A: Patients receive oral temozolomide once a day on days 1-5 and bortezomib IV on days 2, 5, 9, and 12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. GROUP B: Patients receive temozolomide and bortezomib as in group A. Cohorts of patients in both groups receive escalating doses of both study drugs until the maximum tolerated doses are determined. All patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for bortezomib concentration (groups A and B) and trough levels of anticonvulsants (group A only).
Receives: Drug: bortezomib; Drug: temozolomide; Other: pharmacological study

What is being measured

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

  1. Dose-limiting toxicity and maximum tolerated dose

    Measured: 28 days

Secondary outcomes (3)
  1. Pharmacokinetics

    Measured: Day 9

  2. Confirmed complete or partial response

    Measured: 6 months

  3. Percentage of patients with 6-month progression-free survival

    Measured: 6 months

Timeline

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

  1. First posted16 Oct 2007 (estimated)
  2. Study startJan 2005
  3. Primary completionJan 2012
  4. Study completionJan 2012

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
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00544284
Sponsor's protocol ID
04032
Other IDs
P30CA033572, CHNMC-04032, CDR0000570245
Status last verified
Feb 2013
First submitted
13 Oct 2007
Last updated
15 Feb 2013
Results posted
No

Publications

  • Portnow J, Frankel P, Koehler S, Twardowski P, Shibata S, Martel C, Morgan R, Cristea M, Chow W, Lim D, Chung V, Reckamp K, Leong L, Synold TW. A phase I study of bortezomib and temozolomide in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2012 Feb;69(2):505-14. doi: 10.1007/s00280-011-1721-x. Epub 2011 Aug 18.

    PubMed 21850464

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing bortezomib, temozolomide and pharmacological study in people with Brain and Central Nervous System Tumors and Lymphoma, run by City of Hope Medical Center 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 14 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: finished, as of the sponsor's last update on 15 Feb 2013. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Dose-limiting toxicity and maximum tolerated dose (time frame: 28 days). 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 NCT00544284, which also lists 1 linked publication.

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 15 Feb 2013.

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