NCT00544284

Brief 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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
25

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jan 2005

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2005

Completed
2.8 years until next milestone

First Submitted

Initial submission to the registry

October 13, 2007

Completed
3 days until next milestone

First Posted

Study publicly available on registry

October 16, 2007

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2012

Completed
Last Updated

February 15, 2013

Status Verified

February 1, 2013

Enrollment Period

7 years

First QC Date

October 13, 2007

Last Update Submit

February 14, 2013

Conditions

Keywords

adult glioblastomaadult anaplastic astrocytomaadult giant cell glioblastomarecurrent adult brain tumoradult gliosarcomaadult mixed gliomaadult anaplastic oligodendrogliomaprimary central nervous system lymphomaadult diffuse astrocytomaadult brain stem gliomaadult central nervous system germ cell tumoradult choroid plexus tumoradult craniopharyngiomaadult ependymoblastomaadult medulloblastomaadult supratentorial primitive neuroectodermal tumor (PNET)adult anaplastic ependymomaadult ependymomaadult myxopapillary ependymomaadult subependymomaadult anaplastic meningiomaadult melanocytic lesionadult meningeal hemangiopericytomaadult grade I meningiomaadult grade II meningiomaadult grade III meningiomaadult papillary meningiomaadult oligodendrogliomaadult pineoblastomaadult pineocytomatumors metastatic to brainunspecified adult solid tumor, protocol specificadult pilocytic astrocytomaadult subependymal giant cell astrocytoma

Outcome Measures

Primary Outcomes (1)

  • Dose-limiting toxicity and maximum tolerated dose

    28 days

Secondary Outcomes (3)

  • Pharmacokinetics

    Day 9

  • Confirmed complete or partial response

    6 months

  • Percentage of patients with 6-month progression-free survival

    6 months

Study Arms (1)

Treatment (temozolomide, bortezomib)

EXPERIMENTAL

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).

Drug: bortezomibDrug: temozolomideOther: pharmacological study

Interventions

Treatment (temozolomide, bortezomib)
Treatment (temozolomide, bortezomib)
Treatment (temozolomide, bortezomib)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • 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

You may not qualify if:

  • 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
  • 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:
  • 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
  • Patients enrolled on another clinical trial
  • HIV-positive patients on antiretroviral therapy
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

City of Hope Medical Group

Pasadena, California, 91105, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Central Nervous System NeoplasmsLymphomaNeoplasm MetastasisGlioblastomaAstrocytomaBrain NeoplasmsGliosarcomaGliomaOligodendrogliomaChoroid Plexus NeoplasmsCraniopharyngiomaNeuroectodermal Tumors, PrimitiveMedulloblastomaEpendymomaGlioma, SubependymalMeningiomaPinealoma

Interventions

BortezomibTemozolomide

Condition Hierarchy (Ancestors)

Nervous System NeoplasmsNeoplasms by SiteNeoplasmsNervous System DiseasesNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms, Glandular and EpithelialNeoplasms, Nerve TissueBrain DiseasesCentral Nervous System DiseasesCerebral Ventricle NeoplasmsNeoplasms, Vascular TissueMeningeal Neoplasms

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsDacarbazineTriazenesImidazolesAzoles

Study Officials

  • Jana Portnow, MD

    City of Hope Comprehensive Cancer Center

    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

October 13, 2007

First Posted

October 16, 2007

Study Start

January 1, 2005

Primary Completion

January 1, 2012

Study Completion

January 1, 2012

Last Updated

February 15, 2013

Record last verified: 2013-02

Locations