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

NCT ID: NCT00998010

Last Updated: 2020-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-03
• Study Completion Date: 2018-04-20

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.

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

bortezomib + temozolomide+ radiation therapy

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility 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])

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: collaborator

Jonsson Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Albert Lai, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ronald Reagan UCLA Medical Center

Locations

University of California Los Angeles

Los Angeles, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

UCLA-X05303

Identifier Type: -

Identifier Source: secondary_id

CDR0000657015

Identifier Type: -

Identifier Source: secondary_id

MILLENNIUM-UCLA-X05303

Identifier Type: -

Identifier Source: secondary_id

09-03-084

Identifier Type: OTHER

Identifier Source: secondary_id

11-002222

Identifier Type: -

Identifier Source: org_study_id