Bortezomib, Temozolomide, and Regional Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Jonsson Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00998010
First received: October 17, 2009
Last updated: May 27, 2014
Last verified: May 2014
  Purpose

RATIONALE: Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. 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. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bortezomib together with temozolomide and radiation therapy may kill more tumor cells and allow doctors to save the part of the body where the cancer started.

PURPOSE: This phase II trial is studying the side effects and how well bortezomib works when given together with temozolomide and regional radiation therapy in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma.


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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Velcade (Bortezomib) in Combination With Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients With Newly-diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • Time to progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Tumor response as assessed by MRI and neurologic exam [ Time Frame: After radiation is completed, MRI every 8 weeks, neurologic exam every 4 weeks. ] [ Designated as safety issue: No ]
    MRI will be done 2 weeks after completion of radiation and then every 8 weeks. Neurologic exam to be performed every 2 weeks during radiation therapy, then every every 4 weeks after radiation is completed.


Estimated Enrollment: 70
Study Start Date: June 2011
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental
Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42.Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5.Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
Drug: bortezomib + temozolomide+ radiation therapy
Patients will be treated with Bortezomib at 1.3 mg/m2 IV on days1,4,8,11,29,32,36 and 39 and Temozolomide on 75mg/m2 daily during radiation. External beam fractionated regional radiation will be given on consecutive week days at 200cGy daily doses to a total dose of 6000 cGy.

Detailed Description:

OBJECTIVES:

Primary

  • Estimate the overall survival at 2 years of patients with newly diagnosed glioblastoma multiforme treated with bortezomib in combination with temozolomide and regional radiotherapy followed by maintenance therapy comprising bortezomib and temozolomide.

Secondary

  • Investigate further the safety and tolerability of this regimen in these patients.
  • Determine the molecular characterization of tumor tissue and correlate these findings with response.

OUTLINE: This is a multicenter study.

  • Adjuvant chemotherapy: Patients receive bortezomib IV on days 1, 4, 8, 11, 29, 32, 36, and 39 and oral temozolomide on days 1-42. Patients undergo external-beam fractionated regional radiotherapy 5 days a week for 6 weeks in the absence of disease progression or unacceptable toxicity.
  • Maintenance: Beginning 2-6 weeks after radiotherapy, patients receive bortezomib IV on days 1, 4, 8, and 11 and oral temozolomide on days 1-5. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Tumor tissue samples are collected at baseline (from surgery) and periodically during study for further analysis.

After completion of study therapy, patients are followed up periodically.

  Eligibility

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

Inclusion Criteria:

  • Must be >- 18 years old, with a life expectancy > 8 weeks
  • Histologically confirmed intracranial glioblastoma multiforme (GBM) or gliosarcoma
  • Must submit an unstained paraffin block or slides from surgical procedure
  • Patients without prior treatment and with prior diagnosis of lower-grade gliomas that have been upgraded to GBM after repeated resection allowed
  • At least 21 days since cranial MRI or contrast CT scan OR ≥ 96 hours since cranial MRI or contrast CT scan for patients who underwent surgical resection
  • Measurable or assessable disease
  • Voluntary written informed consent obtained before performance of any study related procedure not part of normal medical care.
  • Karnofsky performance status > 60%
  • WBC ≥ 3,000/mm^3
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 10 g/dL (transfusion allowed)
  • Bilirubin < 2.5 times upper limit of normal (ULN)
  • SGOT < 2.5 times ULN
  • Creatinine < 1.5 mg/dL
  • Creatinine clearance ≥ 20 mL/minute
  • Serum sodium > 130 mmol/L
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients on EIAED must be transitioned to non-EAIED for ≥ 2 weeks
  • Concurrent full-dose warfarin or its equivalent (e.g., unfractionated and/or low molecular weight heparin) allowed

Exclusion Criteria:

  • peripheral neuropathy ≥ grade 2
  • Myocardial infarction within the past 6 months
  • NYHA class III or IV heart failure
  • Uncontrolled angina
  • Severe uncontrolled ventricular arrhythmias
  • Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
  • hypersensitivity to bortezomib, boron, or mannitol
  • serious medical or psychiatric illness that would interfere with study participation including, but not limited to, any of the following:
  • Ongoing or active infection requiring IV antibiotics
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • Disorders associated with a significant immunocompromised state (e.g., HIV, systemic lupus erythematosus)
  • history of stroke within the past 6 months
  • other malignancy within the past 3 years except completely resected basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy (i.e., cervical cancer), or low-risk prostate cancer after curative therapy
  • significant medical illness that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
  • disease that will obscure toxicity or dangerously alter drug metabolism
  • viral hepatitis (HBV surface antigen positive) or active hepatitis C infection
  • Prior or concurrent corticosteroids, automated external defibrillator, analgesics, and other drugs to treat symptoms or prevent complications allowed
  • concurrent investigational drugs that must be stopped at least 4 months prior to therapy.
  • prior radiotherapy to the brain
  • prior cytotoxic or noncytotoxic drug therapy or experimental drug therapy (including chemotherapy, hormonal therapy, or immunotherapy) directed against the brain tumor
  • prior polifeprosan 20 with carmustine implant (Gliadel wafer)
  • concurrent stereotactic radiosurgery or brachytherapy
  • concurrent sargramostim
  • concurrent inducers of CYP450 3A4 (e.g., enzyme-inducing anti-epileptic drugs [EIAED])
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00998010

Contacts
Contact: Albert Lai, M.D. 310 825 5321

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Albert Lai, M.D.    310-825-5321      
Principal Investigator: Albert Lai, M.D.         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Albert Lai, MD, PhD Ronald Reagan UCLA Medical Center
  More Information

Additional Information:
No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00998010     History of Changes
Other Study ID Numbers: CDR0000657015, P30CA016042, UCLA-X05303, 09-03-084, MILLENNIUM-UCLA-X05303
Study First Received: October 17, 2009
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Glioblastoma
Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Bortezomib
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014