Glioblastoma MultiformePhase 1NCT01435395
Trial of Temozolomide, Bevacizumab Plus Bortezomib for Recurrent Glioblastoma Multiforme
A Phase 1 study testing Temozolomide, bevacizumab and bortezomib in people with Glioblastoma Multiforme, run by Emory University at 2 sites in United States.
Trial summary
This is a single-center (Emory University), open-label, single arm, phase I study to assess safety and toxicity of bortezomib in combination with bevacizumab and escalating doses of temozolomide for patients with recurrent glioblastoma multiforme. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Temozolomide, bevacizumab and bortezomib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2011to Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Age 18 years or more.
- Patients must have histologically confirmed diagnosis of a recurrent/progressive WHO grade IV malignant gliomas (glioblastoma multiforme and gliosarcoma).
- Patients must have measurable progressive or recurrent disease by MRI within 2 weeks of starting treatment.
- No prior bortezomib is allowed.
- An interval of at least 6 weeks between prior surgical resection, 4 weeks from the end of prior radiotherapy.
- Patients must be at least 10 days off any enzyme inducing anti-epileptic drugs (EIAEDs) of the cytochrome P450 (CYP-450) such as phenytoin, carbamazepine, phenobarbital.
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- Karnofsky performance status score of 60 or more.
- Patients must have recovered from toxicity of prior therapy.
- Hematocrit > 29%, absolute neutrophil count (ANC) > 1,500 cells/microliter, platelets > 125,000 cells/microliter for 14 days prior to treatment initiation.
- Serum creatinine < 1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin < 1.5 times upper limit of normal.
- Prothrombin time/international normalized ratio (PT INR) < 1.4.
- An interval of at least 3 months from the completion of most recent radiation therapy. At least 4 weeks from a non-nitrosourea chemotherapy regimen and at least 6 weeks from a nitrosourea containing regimen.
- For patients on corticosteroids, they must have been on a stable dose for 1 week prior to entry if clinically recommended.
- May have up to three biological therapies.
- Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of the study.
Who cannot join
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
- Greater than three prior recurrences.
- Enzyme-inducing anti-epileptic drugs (EIAEDs) of the CYP-450 such as phenytoin, carbamazepine, phenobarbital.
- Patients receiving concurrent investigational drugs.
- Evidence of central nervous system (CNS) hemorrhage on baseline MRI or CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months).
- History of stroke within six months.
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- Requires therapeutic anti-coagulation.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics and psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state.
- Patient has a calculated or measured creatinine clearance of < 20 mL/minute within 14 days prior to treatment initiation.
- Patient has greater or equal to Grade 2 peripheral neuropathy within 14 days before enrollment.
- Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (Appendix), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
- Patient has hypersensitivity to bortezomib, boron, or mannitol.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs within 14 days of treatment initiation
- Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. Patients with prior malignancies must be disease free for at least 5 years.
- Serious, non-healing wound, active ulcer, or untreated bone fracture. Bone fractures must be healed.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
About this study
Official title: Phase I Trial of Temozolomide, Bevacizumab Plus Bortezomib for Patients With Recurrent Glioblastoma Multiforme
This is a single-center (Emory University), open-label, single arm, phase I study to assess safety and toxicity of bortezomib in combination with bevacizumab and escalating doses of temozolomide for patients with recurrent glioblastoma multiforme. Patients requiring anti-epileptic medications will have to be at least 10 days off EIAEDs. Only non-EIAEDs are accepted.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Temozolomide, bevacizumab and bortezomib
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temozolomide, bevacizumab and bortezomibDrug
Escalating temozolomide with standard dose bevacizumab and bortezomib
| Study group | Role | What they receive |
|---|---|---|
| Therapy | Experimental | Therapy with temozolomide, bevacizumab and bortezomib Receives: Drug: Temozolomide, bevacizumab and bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of progressive disease, complete or partial responses
Complete or partial responses will be based upon major changes in tumor size on the Gd-MRI scan compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with the smallest measurements.
Measured: 6 weeks
Secondary outcomes (1)
Assess the time to progression
Six month progression-free survival and overall survival of patients completing one cycle of the investigational therapy.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2011 (estimated)
- Study startDec 2011
- Primary completionApr 2016
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough, Genentech, Inc., Millennium Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Jeffrey James Olson, Emory University
- Investigators
- Jeffrey J. Olson, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01435395
- Sponsor's protocol ID
- IRB00014595
- Other IDs
- WCI1837-10
- Status last verified
- Apr 2016
- First submitted
- 14 Sep 2011
- Last updated
- 27 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Temozolomide, Bevacizumab Plus Bortezomib for Patients With Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT01435395
- Acronym / sponsor ID
- IRB00014595
- Conditions
- Glioblastoma Multiforme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Schering-Plough, Genentech, Inc., Millennium Pharmaceuticals, Inc.
- Study start
- Dec 2011
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 16 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-center (Emory University), open-label, single arm, phase I study to assess safety and toxicity of bortezomib in combination with bevacizumab and escalating doses of temozolomide for patients with recurrent glioblastoma multiforme. Patients requiring anti-epileptic medications will have to be at least 10 days off EIAEDs. Only non-EIAEDs are accepted.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Therapy | Experimental | Drug: Temozolomide, bevacizumab and bortezomibTherapy with temozolomide, bevacizumab and bortezomib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age 18 years or more.
- Patients must have histologically confirmed diagnosis of a recurrent/progressive WHO grade IV malignant gliomas (glioblastoma multiforme and gliosarcoma).
- Patients must have measurable progressive or recurrent disease by MRI within 2 weeks of starting treatment.
- No prior bortezomib is allowed.
- An interval of at least 6 weeks between prior surgical resection, 4 weeks from the end of prior radiotherapy.
Key exclusion criteria (17 listed)
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
- Greater than three prior recurrences.
- Enzyme-inducing anti-epileptic drugs (EIAEDs) of the CYP-450 such as phenytoin, carbamazepine, phenobarbital.
- Patients receiving concurrent investigational drugs.
- Evidence of central nervous system (CNS) hemorrhage on baseline MRI or CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months).
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 |
|---|---|---|
| Temozolomide, bevacizumab and bortezomibEscalating temozolomide with standard dose bevacizumab and bortezomib | Drug | Therapy |
Primary outcome
Determination of progressive disease, complete or partial responses
Time frame: 6 weeks
Complete or partial responses will be based upon major changes in tumor size on the Gd-MRI scan compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with the smallest measurements.
1 secondary outcome
Assess the time to progression
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2016.
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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.
Jeffrey J. Olson, MD principal investigator
Emory University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Temozolomide, bevacizumab and bortezomib in people with Glioblastoma Multiforme, run by Emory University at 2 sites 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 17 inclusion and 17 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 27 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determination of progressive disease, complete or partial responses (time frame: 6 weeks). 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 27 Apr 2016.