Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide - Full Text View

Purpose

Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving bortezomib together with temozolomide after surgery may kill any tumor cells that remain after surgery.

This phase II trial is studying how well giving bortezomib before surgery followed by giving bortezomib together with temozolomide after surgery works in treating patients with recurrent malignant glioma.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors	Drug: bortezomib Drug: temozolomide	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II Trial Evaluating the Effects of Bortezomib in Patients With Recurrent Malignant Gliomas Treated Prior to Surgery and Then Bortezomib and Temozolomide Post-operatively

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Temozolomide Bortezomib

U.S. FDA Resources

Further study details as provided by Northwestern University:

Primary Outcome Measures:

Correlative Profiles with therapy response and patient survival. [ Time Frame: Samples drawn pre-surgery, Bortezomib treatment day 1, Drawn prior to surgery, Day prior to treatment post surgery, and Day of MRI every cycle POST-surgery, tissue evaluated at study completion ] [ Designated as safety issue: No ]
To determine the effects of Bortezomib on the endogenous modulators of NF-Kappa B pathways, especially NFKBIA, via novel assay technology, and correlate profiles with therapy response and patient survival.

Secondary Outcome Measures:

6 month progression-free survival rate. [ Time Frame: Screening/Baseline, Day 1, 4, 8 pre-surgery, cycle 1 and even cycles ] [ Designated as safety issue: No ]
6 month progression-free survival rate.
Response rate (complete or partial response) [ Time Frame: Day 1, 4, 8 pre-surgery, cycle 1 and even cycles ] [ Designated as safety issue: No ]
To determine response rates for patients with residual tumor post operatively.
Toxicity [ Time Frame: Day 1, 4, 8 pre-surgery, cycle 1 and even cycles ] [ Designated as safety issue: Yes ]
To record the toxicities of Temozolomide and Bortezomib.
Pharmacokinetics [ Time Frame: Day 1, 4, 8 pre-surgery, cycle 1 and even cycles ] [ Designated as safety issue: No ]
To determine MGMT methylation status as well as other methylation patterns in plasma and determine tumor tissue PK of Bortezomib.

Estimated Enrollment:	29
Study Start Date:	May 2009
Estimated Study Completion Date:	May 2014
Estimated Primary Completion Date:	December 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Bortezomib and Temozolomide An injection of bortezomib will be given on Days 1, 4, and 8. Then then have standard of care surgery on Day 8 or 9 to remove the tumor. Once recovered from surgery, temozolomide will be taken by mouth on Days 1-7 and 14-21, and then given an injection of bortezomib on Days 7 and 21 of every 28 day cycle (4 weeks).	Drug: bortezomib An injection of bortezomib will be given on Days 1, 4, and 8. Then then have standard of care surgery on Day 8 or 9 to remove the tumor. Once recovered from surgery, temozolomide will be taken by mouth on Days 1-7 and 14-21, and then given an injection of bortezomib on Days 7 and 21 of every 28 day cycle (4 weeks). Other Name: Velcade Drug: temozolomide An injection of bortezomib will be given on Days 1, 4, and 8. Then then have standard of care surgery on Day 8 or 9 to remove the tumor. Once recovered from surgery, temozolomide will be taken by mouth on Days 1-7 and 14-21, and then given an injection of bortezomib on Days 7 and 21 of every 28 day cycle (4 weeks). Other Name: Temodar

Arms

Assigned Interventions

Experimental: Bortezomib and Temozolomide

An injection of bortezomib will be given on Days 1, 4, and 8. Then then have standard of care surgery on Day 8 or 9 to remove the tumor. Once recovered from surgery, temozolomide will be taken by mouth on Days 1-7 and 14-21, and then given an injection of bortezomib on Days 7 and 21 of every 28 day cycle (4 weeks).

Drug: bortezomib

An injection of bortezomib will be given on Days 1, 4, and 8. Then then have standard of care surgery on Day 8 or 9 to remove the tumor. Once recovered from surgery, temozolomide will be taken by mouth on Days 1-7 and 14-21, and then given an injection of bortezomib on Days 7 and 21 of every 28 day cycle (4 weeks).

Other Name: Velcade

Drug: temozolomide

An injection of bortezomib will be given on Days 1, 4, and 8. Then then have standard of care surgery on Day 8 or 9 to remove the tumor. Once recovered from surgery, temozolomide will be taken by mouth on Days 1-7 and 14-21, and then given an injection of bortezomib on Days 7 and 21 of every 28 day cycle (4 weeks).

Other Name: Temodar

Detailed Description:

Patients receive bortezomib IV on days 1, 4, and 8. Patients then undergo surgical resection of the tumor on day 8 or 9.

Beginning approximately 14 days after surgery, patients receive oral temozolomide on days 1-7 and 14-21 and bortezomib IV on days 7 and 21. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Tumor tissue and blood samples are collected periodically for biomarker analysis, gene methylation studies, and pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 2 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologically confirmed malignant glioma, including any of the following subtypes:
- Glioblastoma multiforme
- Gliosarcoma
- Anaplastic astrocytoma
- Anaplastic oligodendroglioma
- Anaplastic mixed oligoastrocytoma
- Malignant astrocytoma not otherwise specified
Must show unequivocal evidence of tumor recurrence or progression by MRI or CT scan with contrast
Candidate for surgery AND requires surgery
- Evaluable or measurable disease following resection of recurrent tumor is not required
Failed prior standard radiotherapy and temozolomide
- Patients who have undergone stereotactic radiosurgery must have confirmation of true progressive disease (rather than radiation necrosis) by PET scan, magnetic resonance spectroscopy (MRS), or magnetic resonance perfusion (MRP) prior to surgery
- Patients with lower-grade gliomas that have undergone radiographic malignant transformation allowed provided they failed radiotherapy (with or without temozolomide) and require surgery
Life expectancy > 12 weeks

Exclusion Criteria:

Not pregnant or nursing
Negative pregnancy test
No other medical issues (e.g., bleeding, infection, HIV, or serious medical or psychiatric illness) that would preclude study therapy
Myocardial infarction within the past 6 months
No other active cancer(s) except non-melanoma skin cancer or carcinoma in situ of the cervix, unless in complete remission and off of all therapy for that cancer for ≥ 3 years
No hypersensitivity to bortezomib, boron, or mannitol
More than 4 weeks since prior radiotherapy
At least 4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas)
At least 3 weeks since prior investigational drugs
At least 2 weeks since prior enzyme-inducing anticonvulsants
Concurrent non-enzyme-inducing anticonvulsants allowed
No other concurrent standard or investigational anticancer treatment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00990652

Locations

United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611

Sponsors and Collaborators

Northwestern University

Millennium Pharmaceuticals, Inc.

Investigators

Principal Investigator:

Jeffrey Raizer, MD

Northwestern University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Jeffrey Raizer, Jeffrey Raizer, MD, Northwestern University
ClinicalTrials.gov Identifier:	NCT00990652 History of Changes
Other Study ID Numbers:	NU 08C5, STU00008280
Study First Received:	October 6, 2009
Last Updated:	March 21, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Keywords provided by Northwestern University:

brain tumor

Additional relevant MeSH terms:

Nervous System Neoplasms
Central Nervous System Neoplasms
Glioma
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

Temozolomide
Dacarbazine
Bortezomib
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protease Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 19, 2013