Adult Giant Cell GlioblastomaPhase 2NCT00238303
Vorinostat in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
A Phase 2 study testing vorinostat and conventional surgery in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- vorinostat and conventional surgery
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 103 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Mar 2010
- 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
- Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme), including gliosarcoma, at primary diagnosis or recurrence
- Progressive or recurrent disease
- Measurable or evaluable disease by MRI or CT scan
- Performance status - ECOG 0-2
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
Show all 33Show fewer
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 8 g/dL
- AST ≤ 3 times upper limit of normal (ULN)
- Bilirubin normal
- Creatinine ≤ 1.5 times ULN
- No myocardial infarction within the past 6 months
- No congestive heart failure
- No life-threatening ventricular arrhythmia requiring ongoing maintenance therapy
- No known HIV positivity
- Not immunocompromised except if related to the use of corticosteroids
- No known hypersensitivity to any of the components of the study drug
- No uncontrolled infection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after completion of study treatment
- No other malignancy
- No other severe disease that would preclude study participation
- Prior adjuvant chemotherapy allowed
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- More than 2 weeks since prior small molecule cell cycle inhibitor
- Concurrent corticosteroids allowed as long as dose has been stable for ≥ 1 week
- At least 8 weeks since prior radiotherapy
- Must have evidence of tumor progression by MRI or CT scan after radiotherapy
- More than 6 weeks since prior stereotactic radiosurgery or interstitial brachytherapy, unless 1 of the following criteria is met:
- There is a separate lesion by MRI outside of the prior treatment field
- There is evidence of recurrent disease by biopsy, MRI spectroscopy, or positron-emission tomography scan
- More than 2 weeks since prior valproic acid
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
North Central Cancer Treatment Group
Rochester, Minnesota, 55905
About this study
Official title: Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma
This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any remaining tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the efficacy of vorinostat (SAHA), in terms of 6-month progression-free survival, in patients with progressive or recurrent glioblastoma multiforme.
II. Determine the safety and toxicity of this drug in these patients.
SECONDARY OBJECTIVES:
- Determine the pharmacokinetics of this drug in these patients. II. Determine the biologic effect of this drug in target tissues, including primary tumor tissue, in these patients.
III. Correlate genetic alteration of tumors with response in patients treated with this drug.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to planned surgery (yes [stratum 1] vs no [stratum 2]) and number of prior chemotherapy regimens for progressive/recurrent disease (≤ 1 [stratum 1A] vs ≥ 2 [stratum 1B]).
STRATUM 1: Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. (not undergoing surgery)
STRATUM 2: Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. (undergoing surgery)
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 5 years.
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Being tested
- vorinostat, conventional surgery
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vorinostatDrug
Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Given orally
conventional surgeryProcedure or surgery
Also called surgery, conventional
Patients undergo surgery to remove tumor
| Study group | Role | What they receive |
|---|---|---|
| Stratum 1 (not undergoing surgery) | Experimental | Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: vorinostat; Procedure: conventional surgery |
| Stratum 2 (undergoing surgery) | Experimental | Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: vorinostat; Procedure: conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Successes (Patients Alive and Progression-free)
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 95% confidence interval estimated by the exact method.
Definition of progression:
Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.
Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
Measured: At 6 months
Secondary outcomes (3)
Survival
Estimated using Kaplan-Meier survival curve.
Measured: From study registration to date of death due to any cause or last follow-up (up to 5 years)
Confirmed Tumor Response
A confirmed tumor response will be defined as an objective status of complete response (CR), partial response (PR), or regression (REGR) on two consecutive evaluations, which include neuroimaging, lasting during a period of at least 6 weeks. Confidence intervals for the true proportion will be calculated using the exact binomial method.
Bidimensionally measurable disease:≥50% reduction in product of perpendicular diameters of contrast enhancement or mass with no new lesions with the patient being on stable or decreased steroid dose.
Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal reduction in size of contrast-enhancement or decrease in mass effect as agreed upon independently by primary physician and quality control physicians; no new lesions. Patient should be on stable or decreased steroid dose.
Measured: Assessed up to 5 years
Time to Progression
Estimated using Kaplan-Meier survival curve.
Definition of progression:
Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions.
Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
Measured: From registration to disease progression (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2005 (estimated)
- Study startSep 2005
- Primary completionJul 2008
- Study completionMar 2010
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 Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 103 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Evanthia Galanis, Principal investigator, North Central Cancer Treatment Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00238303
- Sponsor's protocol ID
- NCI-2009-00646
- Other IDs
- NCI-2009-00646, CDR0000445405, NCCTG-N047B, N047B, N047B, U10CA025224
- Status last verified
- Oct 2011
- First submitted
- 12 Oct 2005
- Last updated
- 23 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT00238303
- Acronym / sponsor ID
- NCI-2009-00646
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 103 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2005
- Primary completion
- Jul 2008 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 13 Oct 2005 (estimated)
- Results
- Posted 10 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well vorinostat works in treating patients with progressive or recurrent glioblastoma multiforme. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving vorinostat before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any remaining tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the efficacy of vorinostat (SAHA), in terms of 6-month progression-free survival, in patients with progressive or recurrent glioblastoma multiforme.
II. Determine the safety and toxicity of this drug in these patients.
SECONDARY OBJECTIVES:
- Determine the pharmacokinetics of this drug in these patients. II. Determine the biologic effect of this drug in target tissues, including primary tumor tissue, in these patients.
III. Correlate genetic alteration of tumors with response in patients treated with this drug.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to planned surgery (yes [stratum 1] vs no [stratum 2]) and number of prior chemotherapy regimens for progressive/recurrent disease (≤ 1 [stratum 1A] vs ≥ 2 [stratum 1B]).
STRATUM 1: Patients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. (not undergoing surgery)
STRATUM 2: Beginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. (undergoing surgery)
Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stratum 1 (not undergoing surgery) | Experimental | Drug: vorinostat, Procedure: conventional surgeryPatients receive oral vorinostat (SAHA) twice daily for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. |
| Stratum 2 (undergoing surgery) | Experimental | Drug: vorinostat, Procedure: conventional surgeryBeginning 3 days prior to surgery, patients receive oral SAHA once or twice daily for a total of 6 doses. Patients then undergo surgery to remove the tumor. Beginning within 1-4 weeks after surgery, patients receive oral SAHA twice daily for 2 weeks. Courses repeat every 3 weeks 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 (33 listed)
- Histologically confirmed grade 4 astrocytoma (glioblastoma multiforme), including gliosarcoma, at primary diagnosis or recurrence
- Measurable or evaluable disease by MRI or CT scan
- Performance status - ECOG 0-2
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| vorinostatAlso: L-001079038, SAHA, suberoylanilide hydroxamic acid, ZolinzaGiven orally | Drug | Stratum 1 (not undergoing surgery), Stratum 2 (undergoing surgery) |
| conventional surgeryAlso: surgery, conventionalPatients undergo surgery to remove tumor | Procedure or surgery | Stratum 1 (not undergoing surgery), Stratum 2 (undergoing surgery) |
Primary outcome
Proportion of Successes (Patients Alive and Progression-free)
Time frame: At 6 months
Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and the Binomial 95% confidence interval estimated by the exact method. Definition of progression: Bidimensionally measurable disease: >25% increase in product of perpendicular diameters of contrast enhancement or mass or appearance of new lesions. Evaluable disease (i.e., contrast enhancing mass on MRI and/or CT that is not bidimensionally measurable but clearly evaluable for response to therapy): unequivocal increase in size of contrast enhancement or increase in mass effect as agreed upon independently by primary physician and quality control physicians: appearance of new lesions.
3 secondary outcomes
Survival
Time frame: From study registration to date of death due to any cause or last follow-up (up to 5 years)
Confirmed Tumor Response
Time frame: Assessed up to 5 years
Time to Progression
Time frame: From registration to disease progression (up to 5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Adult Giant Cell Glioblastoma
Active, not recruitingPhase 1
Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma
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.
Evanthia Galanis principal investigator
North Central Cancer Treatment Group
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 vorinostat and conventional surgery in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) 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 33 inclusion and 0 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 23 May 2014. 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 10 Jul 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?
Proportion of Successes (Patients Alive and Progression-free) (time frame: At 6 months). 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 23 May 2014.