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

Northwestern University

Status and phase: Completed; Phase 2

Conditions: Brain and Central Nervous System Tumors

Treatments: Drug: Bortezomib; Drug: Temozolomide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00990652

STU00008280 (Other Identifier)

NU 08C5

Details and patient eligibility

About

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.

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Bortezomib + Temozolomide

Experimental group

Description:

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.

Treatment:

Drug: Temozolomide

Drug: Bortezomib