Brain TumorPhase 1/2NCT00939991
Suberoylanilide Hydroxamic Acid (SAHA), Bevacizumab, Daily Temozolomide for Recurrent Malignant Gliomas
A Phase 1/2 study testing Vorinostst/Bevacizumab/Temozolomide in people with Brain Tumor and Glioblastoma, run by Katy Peters at 1 site in United States.
Trial summary
This is a Phase I/II open-label, single-arm study among recurrent malignant glioma patients. Patients will be treated with Vorinostat in combination with Bevacizumab (BV) (10 mg/kg) and Temozolomide (T) (50 mg/m2/day) BV is administered every 2 weeks. Temozolomide will be taken orally once every day. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Tumor, Glioblastoma
- What is being tested?
- Vorinostst/Bevacizumab/Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Apr 2013
- Phase
- Phase 1/2
- 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
- Patients must have histologically confirmed diagnosis of malignant glioma and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bidimensional product of enhancement or a new enhancing lesion) following prior therapy. In addition, the following must be met:
- Phase I specific
- WHO grade 3 or 4 malignant glioma Phase II specific
- WHO grade 4 malignant glioma
- No more than 2 prior episodes of disease progression
- Common to both Phase I and Phase II
Show all 20Show fewer
- Age * 18 years
- KPS (Karnofsky Performance Scale) ≥ 70%
- An interval of at least 4 weeks between prior surgical resection or one week from stereotactic biopsy
- An interval of at least 12 weeks from the end of prior radiotherapy unless there is a new area of enhancement consistent with recurrent tumor outside of the radiation field, or there are progressive changes on MRI on at least two consecutive MRI scans at least four weeks apart, or there is biopsy-proven tumor progression
- An interval of at least 4 weeks from prior chemotherapy (6 weeks for nitrosoureas) or investigational agent unless the patient has recovered from all anticipated toxicities associated with that therapy
- Hematocrit ≥ 29%, ANC ≥ 1,000 cells/*l, platelets ≥ 100,000 cells/*l
- Serum creatinine < 1.5 times upper limit of normal, serum SGOT < 2.5 times upper limit of normal and bilirubin < 2.0 times upper limit of normal
- Signed informed consent approved by the Institutional Review Board prior to patient entry
- No evidence of hemorrhage on the baseline MRI or CT scan other than those that are stable grade 1
- If sexually active, patients will take contraceptive measures for the duration of the treatments. Medically acceptable contraceptives include:
- surgical sterilization (such as a tubal ligation, hysterectomy, vasectomy),
- approved hormonal contraceptives (such as birth control pills, patches, implants or injections),
- barrier methods (such as a condom or diaphragm) used with a spermicide, or
- an intrauterine device (IUD).
Who cannot join
- Prior therapy with histone deacetylase inhibitors; valproic acid is not permitted and patients previously treated with valproic acid must be off valproic acid for at least 30 days prior to initiation of study medication
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
- Active infection requiring intravenous antibiotics
- Progression on prior bevacizumab or daily temozolomide
- Grade 3 or greater toxicity related to prior bevacizumab or daily temozolomide therapy
- Requires therapeutic anti-coagulation with warfarin
Show all 14Show fewer
- Life expectancy of <12 weeks
- Active malignancy other than basal or squamous cell skin ca or carcinoma in situ of cervix within 5 years
- Subject recruitment and compensation - subjects will be recruited for this study as follows:
- Upon determination that a subject's tumor histology and/or radiographic findings are compatible with the eligibility criteria of this protocol, the clinical study will be briefly explained to the subject by the subject's physician, who will be a physician at the Brain Tumor Center at Duke.
- If the subject indicates interest in study participation, subject education sheets and the informed consent document will be provided to the subject as these provide the most comprehensive explanation of the study in lay terms.
- If the subject shows continued interest, the PI or designee will thoroughly explain the required elements of the consent form and all aspects of the study to the subject including inclusion/exclusion criteria, risks, benefits, and alternatives to study participation.
- Subjects will not be paid to take part in this research study.
- The list of subjects pre-screened will be kept in an Excel spreadsheet in the study coordinator's office. The PC (personal computer) is on the DUHS (Duke University Health System) network protected by a user ID (identifier) and password and the office is locked when it is unoccupied. All screened subjects who are not enrolled in the study will have all identifiers destroyed immediately.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Phase I/II Study of Bevacizumab Plus Daily Temozolomide and Vorinostat for Recurrent Malignant Glioma Patients
This is a Phase I/II open-label, single-arm study among recurrent malignant glioma patients. Patients will be treated with Vorinostat in combination with Bevacizumab (BV) (10 mg/kg) and Temozolomide (T) (50 mg/m2/day) BV is administered every 2 weeks. Temozolomide will be taken orally once every day. Vorinostat will be taken orally on days 1-7 and 15-21 of each 28-day cycle. In the phase I portion of this study, the dose of Vorinostat will be escalated in successive cohorts of patients to determine the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs). In the phase II portion of this study, the dose of Vorinostat will be the MTD determined in the phase I portion. The primary endpoint of the phase II study is 6-month progression-free survival (PFS) for recurrent GBM (Glioblastoma) patients. This study will be conducted at The Preston Robert Tisch Brain Tumor Center at Duke.
- Conditions
- Brain Tumor, Glioblastoma
- Being tested
- Vorinostst/Bevacizumab/Temozolomide
- Keywords
- GBM
- Medical subject headings
- Brain Neoplasms, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostst/Bevacizumab/TemozolomideDrug
Also called Bevacizumab (Avastin), Temozolomide (Temodar), Vorinostat (Zolinza)
Bevacizumab will be administered intravenously at the dose 10 mg/kg every other week. Temozolomide will be administered on a continuous daily dosing schedule at 50 mg/m2/day. Vorinostat will be administered daily on days 1-7 and 15-21 of each 28 day cycle. The dose of Vorinostat will be escalated in successive cohorts of patients to determine the MTD of this regimen. Bevacizumab doses may be given by the local oncologists under the direction of the Duke investigators.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Phase I- Bevacizumab will be administered intravenously every other week. Temozolomide will be administered on a continuous daily dosing schedule. Vorinostat will be administered daily on days 1-7 and 15-21 of each 28 day cycle. The dose of Vorinostat will be escalated in successive cohorts of patients to determine the MTD of this regimen. Receives: Drug: Vorinostst/Bevacizumab/Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Determination of the Maximum Tolerated Dose (MTD)
The MTD is based upon dose-limiting toxicities (DLTs) experienced during Cycle 1 of treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with at least two patients experiencing DLT at the next higher dose level. Using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, DLTs are defined as: Grade 4 neutropenia lasting greater than 5 days; Grade 3 thrombocytopenia; the occurrence of non-hematologic Grade 3 or greater drug-related adverse events excluding Grade ≥ 3 elevation in alkaline phosphatase, Grade ≥ 3 nausea or vomiting unless occurring despite the use of standard anti-emetics or Grade 3 diarrhea unless occurring despite standard anti-diarrheal therapy; > 14 day delay to re-treat due to failure to resolve drug-related toxicity to re-treatment criteria or pre-treatment baseline.
Measured: Cycle 1 (28 days)
Phase II: 6-month Progression-free Survival (PFS)
Phase II: Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to RANO criteria, or to death due to any cause. Per RANO, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.
Measured: 6 months
Secondary outcomes (4)
Phase II: Radiographic Response.
The percentage of participants with a complete or partial response as determined by modified Response Assessment in Neuro-Oncology (RANO) criteria. A confirmation of response was not required. Complete Response (CR) was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses) and accompanied by a stable or improving neurologic examination. Partial Response (PR) was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids and accompanied by a stable or improving neurologic examination. Tumor assessments were done at baseline, the end of the first cycle (4 weeks), then the end of every second cycle (every 8 weeks) thereafter.
Measured: 3 years
Phase II: Median Progression-free Survival (PFS)
Phase II: Time in months from the start of study treatment to the date of first progression according to RANO criteria, or to death due to any cause. Per RANO, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
Measured: 3 years
Phase II: Median Overall Survival (OS)
Phase II: Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Measured: 3 years
Phase II: Number of Patients With Grade 2 or Greater, Treatment-related Toxicities
Phase II: Number of patients with grade 2 or greater, treatment-related toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2009 (estimated)
- Study startOct 2009
- Primary completionJan 2012
- Study completionApr 2013
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 TumorStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Katy Peters
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Katy Peters, Duke University
- Investigators
- Katherine Peters, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00939991
- Sponsor's protocol ID
- Pro00016446
- Status last verified
- May 2013
- First submitted
- 14 Jul 2009
- Last updated
- 24 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Bevacizumab Plus Daily Temozolomide and Vorinostat for Recurrent Malignant Glioma Patients
- ClinicalTrials.gov ID
- NCT00939991
- Acronym / sponsor ID
- Pro00016446
- Conditions
- Brain Tumor, Glioblastoma
- Keywords
- GBM
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Katy PetersUniversity, hospital or other
- Collaborators
- Genentech, Inc., Merck Sharp & Dohme LLC
- Study start
- Oct 2009
- Primary completion
- Jan 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 15 Jul 2009 (estimated)
- Results
- Posted 24 Jun 2013
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 Phase I/II open-label, single-arm study among recurrent malignant glioma patients. Patients will be treated with Vorinostat in combination with Bevacizumab (BV) (10 mg/kg) and Temozolomide (T) (50 mg/m2/day) BV is administered every 2 weeks. Temozolomide will be taken orally once every day. Vorinostat will be taken orally on days 1-7 and 15-21 of each 28-day cycle. In the phase I portion of this study, the dose of Vorinostat will be escalated in successive cohorts of patients to determine the maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs). In the phase II portion of this study, the dose of Vorinostat will be the MTD determined in the phase I portion. The primary endpoint of the phase II study is 6-month progression-free survival (PFS) for recurrent GBM (Glioblastoma) patients. This study will be conducted at The Preston Robert Tisch Brain Tumor Center at Duke.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Vorinostst/Bevacizumab/TemozolomidePhase I- Bevacizumab will be administered intravenously every other week. Temozolomide will be administered on a continuous daily dosing schedule. Vorinostat will be administered daily on days 1-7 and 15-21 of each 28 day cycle. The dose of Vorinostat will be escalated in successive cohorts of patients to determine the MTD of this regimen. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients must have histologically confirmed diagnosis of malignant glioma and radiographic evidence of recurrence or disease progression (defined as either a greater than 25% increase in the largest bidimensional product of enhancement or a new enhancing lesion) following prior therapy. In addition, the following must be met:
- Phase I specific
- WHO grade 3 or 4 malignant glioma Phase II specific
- WHO grade 4 malignant glioma
- No more than 2 prior episodes of disease progression
Key exclusion criteria (14 listed)
- Prior therapy with histone deacetylase inhibitors; valproic acid is not permitted and patients previously treated with valproic acid must be off valproic acid for at least 30 days prior to initiation of study medication
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
- Active infection requiring intravenous antibiotics
- Progression on prior bevacizumab or daily temozolomide
- Grade 3 or greater toxicity related to prior bevacizumab or daily temozolomide therapy
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 |
|---|---|---|
| Vorinostst/Bevacizumab/TemozolomideAlso: Bevacizumab (Avastin), Temozolomide (Temodar), Vorinostat (Zolinza)Bevacizumab will be administered intravenously at the dose 10 mg/kg every other week. Temozolomide will be administered on a continuous daily dosing schedule at 50 mg/m2/day. Vorinostat will be administered daily on days 1-7 and 15-21 of each 28 day cycle. The dose of Vorinostat will be escalated in successive cohorts of patients to determine the MTD of this regimen. Bevacizumab doses may be given by the local oncologists under the direction of the Duke investigators. | Drug | 1 |
Primary outcome
Phase I: Determination of the Maximum Tolerated Dose (MTD)
Time frame: Cycle 1 (28 days)
The MTD is based upon dose-limiting toxicities (DLTs) experienced during Cycle 1 of treatment. The MTD is the dose level at which 0/6 or 1/6 patients experience DLT with at least two patients experiencing DLT at the next higher dose level. Using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, DLTs are defined as: Grade 4 neutropenia lasting greater than 5 days; Grade 3 thrombocytopenia; the occurrence of non-hematologic Grade 3 or greater drug-related adverse events excluding Grade ≥ 3 elevation in alkaline phosphatase, Grade ≥ 3 nausea or vomiting unless occurring despite the use of standard anti-emetics or Grade 3 diarrhea unless occurring despite standard anti-diarrheal therapy; > 14 day delay to re-treat due to failure to resolve drug-related toxicity to re-treatment criteria or pre-treatment baseline.
Phase II: 6-month Progression-free Survival (PFS)
Time frame: 6 months
Phase II: Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to RANO criteria, or to death due to any cause. Per RANO, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.
4 secondary outcomes
Phase II: Radiographic Response.
Time frame: 3 years
Phase II: Median Progression-free Survival (PFS)
Time frame: 3 years
Phase II: Median Overall Survival (OS)
Time frame: 3 years
Phase II: Number of Patients With Grade 2 or Greater, Treatment-related Toxicities
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2013.
- 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.
Katherine Peters, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vorinostst/Bevacizumab/Temozolomide in people with Brain Tumor and Glioblastoma, run by Katy Peters 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 20 inclusion and 14 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 24 Jun 2013. 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 combined 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.
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 24 Jun 2013). 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?
Phase I: Determination of the Maximum Tolerated Dose (MTD) (time frame: Cycle 1 (28 days)). The study lists 2 primary outcomes in all. 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 24 Jun 2013.