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

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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% - White Blood Count (WBC) ≥ 3,000/mm^3.
  • - absoulte neutrophil count(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) - serum glutamic-oxaloacetic transaminase (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 Enzyme-Inducing Antiepileptic Drugs (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.
  • - New York Heart Association (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])

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT00998010
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Jonsson Comprehensive Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Albert Lai, MD, PhD
Principal Investigator Affiliation Ronald Reagan UCLA Medical Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain and Central Nervous System Tumors
Additional Details

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.

Arms & Interventions

Arms

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.

Interventions

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 200 centigray (cGy) daily doses to a total dose of 6000 cGy.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of California Los Angeles, Los Angeles, California

Status

Address

University of California Los Angeles

Los Angeles, California, 90095