Brain and Central Nervous System TumorsPhase 2NCT00998010
Bortezomib, Temozolomide, and Regional Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
A Phase 2 study testing bortezomib + temozolomide+ radiation therapy in people with Brain and Central Nervous System Tumors, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- bortezomib + temozolomide+ radiation therapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Oct 2011to 20 Apr 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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 locations and contacts
1 site in 1 country.
United States1 site
University of California Los Angeles
Los Angeles, California, 90095
About this study
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
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.
Read the 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
- Being tested
- bortezomib + temozolomide+ radiation therapy
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomib + temozolomide+ radiation therapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: bortezomib + temozolomide+ radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 2 years
Secondary outcomes (4)
Toxicity Assessed According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.
Measured: 2 years
Time to Progression
Median time to tumor progression. Because many newly-diagnosed patients are likely not to have evaluable disease due to gross total resections. A 7-point scale was used to guide Magnetic resonance imaging (MRI) assessment to determine progression in this study. A -2 or -3 assessment will be taken as progression.
The 7-point scale is listed below. complete resolution of tumor: 3 tumor definitely smaller: 2 tumor probably smaller: 1 tumor unchanged: 0 tumor probably worse: -1 tumor definitely worse: -2 new lesion: -3
Measured: From the completion of radiation treatment to tumor progression
Survival at 1 Year
Overall Survival at 12 months from completion of radiation treatment
Measured: 1 year
Tumor Progression as Assessed by Magnetic Resonance Imaging (MRI) and Neurologic Exam
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.
Measured: at 6, 12, 18 and 24 months from completion of radiation treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2009 (estimated)
- Study start3 Oct 2011
- Primary completion29 Mar 2016
- Study completion20 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Albert Lai, MD, PhD, Principal investigator, Ronald Reagan UCLA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00998010
- Sponsor's protocol ID
- 11-002222
- Other IDs
- UCLA-X05303, CDR0000657015, MILLENNIUM-UCLA-X05303, 09-03-084
- Status last verified
- May 2019
- First submitted
- 17 Oct 2009
- Last updated
- 28 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00998010
- Acronym / sponsor ID
- 11-002222
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult giant cell glioblastoma, adult glioblastoma, adult gliosarcoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- 3 Oct 2011 (actual)
- Primary completion
- 29 Mar 2016 (actual)
- Study completion
- 20 Apr 2018 (actual)
- First posted
- 20 Oct 2009 (estimated)
- Results
- Posted 17 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: bortezomib + temozolomide+ radiation therapyPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- 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
Key exclusion criteria (24 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| bortezomib + temozolomide+ radiation therapyPatients 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. | Drug | Experimental |
Primary outcome
Overall Survival
Time frame: 2 years
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).
4 secondary outcomes
Toxicity Assessed According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.
Time frame: 2 years
Time to Progression
Time frame: From the completion of radiation treatment to tumor progression
Survival at 1 Year
Time frame: 1 year
Tumor Progression as Assessed by Magnetic Resonance Imaging (MRI) and Neurologic Exam
Time frame: at 6, 12, 18 and 24 months from completion of radiation treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Lai, MD, PhD principal investigator
Ronald Reagan UCLA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing bortezomib + temozolomide+ radiation therapy in people with Brain and Central Nervous System Tumors, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2020.