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

NCT00998010 | Completed Phase 2 Results DMC

• 5 other identifiers: 11-002222UCLA-X05303CDR0000657015MILLENNIUM-UCLA-X0530309-03-084
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult giant cell glioblastoma; adult glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Estimate the overall survival in subjects with newly-diagnosed glioblastoma (GBM) treated with bortezomib/temozolomide/radiation followed by bortezomib/temozolomide for 24 cycles until progression is detected or for up to 24 cycles (\~2 years).

  2 years

Secondary Outcomes (4)

• Toxicity Assessed According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.

  2 years

• Time to Progression

  From the completion of radiation treatment to tumor progression

• Survival at 1 Year

  1 year

• Tumor Progression as Assessed by Magnetic Resonance Imaging (MRI) and Neurologic Exam

  at 6, 12, 18 and 24 months from completion of radiation treatment.

Study Arms (1)

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

Interventions

bortezomib + temozolomide+ radiation therapy DRUG

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.

Experimental

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Enrolls newly diagnosed GBM patient and requires collection of frozen and paraffin tumor tissue in all study patients from original surgery. Tissues for methylated (MGHT) and isocitrate dehydrogengenotyping and correlative molecular characterization

Results Point of Contact

• Title: Mark Glover
• Organization: University of California at Los Angeles

mglover@mednet.ucla.edu

(310) 794-8742

Study Officials

• Albert Lai, MD, PhD

  Ronald Reagan UCLA Medical Center

  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: SPONSOR

Study Record Dates

• First Submitted: October 17, 2009
• First Posted: October 20, 2009
• Study Start: October 3, 2011
• Primary Completion: March 29, 2016
• Study Completion: April 20, 2018
• Last Updated: August 28, 2020
• Results First Posted: July 17, 2020

Record last verified: 2019-05

Locations

US (1)