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

NCT00990652 | Completed Phase 2 Results DMC

• 2 other identifiers: NU 08C5STU00008280
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

brain tumor

Outcome Measures

Primary Outcomes (1)

• Number of Patients Surviving Without Disease Progression After 6 Months

  Patients will be monitored from date of first treatment to the date of first observation of progressive disease, non-reversible neurologic progression or increasing steroid requirements, death due to any cause, or early discontinuation of treatment. Progression-free survival will be defined as the absence of any of the above after 6 months. Progression (defined by MacDonald Criteria) is a 25% increase in the sum of products of all measurable lesions over smallest sum observed compared to baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to the cancer).

  From date of first treatment until disease progression, death, or early discontinuation of treatment (up to 24 months)

Secondary Outcomes (4)

• Number of Participants Achieving a Response to Treatment (Either Complete or Partial Response) as Defined by MacDonald Criteria

  Day of treatment post-surgery and then approximately every 8 weeks thereafter until off treatment

• Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 3.0)

  Days 1, 4, 8 pre-surgery, and then at the start of every cycle (approximately every 4 weeks) post-surgery while on treatment

• Overall Survival (in Days)

  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

• Overall Survival Rate at 6 Months

  After 6 months on study

Other Outcomes (3)

• Correlation of Expression of NFKBIA Gene With Response to Therapy and Survival.

  Tissue samples for analysis were obtained on the day of surgery for all patients

• Change in MGMT Methylation Status as Well as Other Methylation Patterns in Plasma

  Blood samples drawn on days 1, 4, and 8 pre-surgery, and then prior to cycle 1 and every 2 cycles thereafter

• Pharmacokinetics of Bortezomib in Tumor Tissue Taken at the Time of Surgery.

  Tissue sample taken at the time of surgery for all patients.

Study Arms (1)

Bortezomib + Temozolomide

EXPERIMENTAL

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.

Drug: Bortezomib; Drug: Temozolomide

Interventions

Bortezomib 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).

Also known as: Velcade

Bortezomib + Temozolomide

Temozolomide DRUG

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

Also known as: Temodar

Bortezomib + Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Northwestern University: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Brain Neoplasms

Interventions

Bortezomib; Temozolomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dacarbazine; Triazenes; Imidazoles; Azoles

Results Point of Contact

• Title: Jeffrey Raizer, MD
• Organization: Northwestern University

jraizer@nmff.org

312-503-4724

Study Officials

• Jeffrey Raizer, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Jeffrey Raizer, MD

Study Record Dates

• First Submitted: October 6, 2009
• First Posted: October 7, 2009
• Study Start: May 1, 2009
• Primary Completion: April 1, 2011
• Study Completion: October 1, 2012
• Last Updated: January 13, 2014
• Results First Posted: January 13, 2014

Record last verified: 2013-12

Locations

US (1)