Clinical trial NCT00990652: Presurgery Bortezomib for Recurrent Malignant Gliomas Followed by Postop Bortezomib & Temozolomide
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: brain tumor
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
First posted: 2009-10-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Patients Surviving Without Disease Progression After 6 Months
timeFrame: From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months)
Secondary outcomes:
measure: Number of Participants Achieving a Response to Treatment (Either Complete or Partial Response) as Defined by MacDonald Criteria
timeFrame: Day of treatment post-surgery and then approximately every 8 weeks thereafter until off treatment
measure: Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)
timeFrame: Days 1, 4, 8 pre-surgery, and then at the start of every cycle (approximately every 4 weeks) post-surgery while on treatment
measure: Overall Survival (in Days)
timeFrame: Days 1, 4, 8 pre-surgery, once per cycle (every 4 weeks) while on treatment post-surgery, and then every 3 months up to 2 years during follow-up
measure: Overall Survival Rate at 6 Months
timeFrame: After 6 months on study
Other outcomes:
measure: Correlation of Expression of NFKBIA Gene With Response to Therapy and Survival.
timeFrame: Tissue samples for analysis were obtained on the day of surgery for all patients
measure: Change in MGMT Methylation Status as Well as Other Methylation Patterns in Plasma
timeFrame: Blood samples drawn on days 1, 4, and 8 pre-surgery, and then prior to cycle 1 and every 2 cycles thereafter
measure: Pharmacokinetics of Bortezomib in Tumor Tissue Taken at the Time of Surgery.
timeFrame: Tissue sample taken at the time of surgery for all patients.
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Jeffrey Raizer, MD
role: PRINCIPAL_INVESTIGATOR
References: