Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide

NCT ID: NCT00990652

Last Updated: 2014-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-05-31
• Study Completion Date: 2012-10-31

Brief Summary

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.

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib + Temozolomide

Patients receive an injection of bortezomib 1.7mg/m\^2 on days 1, 4 and 8. Patients then undergo their standard of care surgery on day 8 or 9 to remove the tumor. Once recovered from surgery, patients receive combination treatment with temozolomide and bortezomib in periods called cycles (1 cycle = 28 days). Temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle, and bortezomib injections are given on days 7 and 21 of each cycle.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Before surgery, an injection of bortezomib is given on days 1, 4, and 8. After surgery, bortezomib is given on days 7 and 21 of each cycle (1 cycle = 28 days).

Temozolomide

Intervention Type: DRUG

After surgery, temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle (1 cycle = 28 days).

Interventions

Bortezomib

Before surgery, an injection of bortezomib is given on days 1, 4, and 8. After surgery, bortezomib is given on days 7 and 21 of each cycle (1 cycle = 28 days).

Intervention Type: DRUG

Temozolomide

After surgery, temozolomide is taken by mouth on days 1-7 and 14-21 of each cycle (1 cycle = 28 days).

Intervention Type: DRUG

Other Intervention Names

Velcade; Temodar

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey Raizer

Jeffrey Raizer, MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Raizer, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Countries

United States

Other Identifiers

STU00008280

Identifier Type: OTHER

Identifier Source: secondary_id

NU 08C5

Identifier Type: -

Identifier Source: org_study_id