GlioblastomaPhase 1NCT00762255
A Phase I Trial of Vorinostat in Combination With Bevacizumab & Irinotecan in Recurrent Glioblastoma
A Phase 1 study testing Vorinostat, Bevacizumab and Irinotecan in people with Glioblastoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of the this study is to see if an investigations cancer treatment called vorinostat can be combined with the irinotecan/bevacizumab regimen safely. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Vorinostat, Bevacizumab and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2008to Jul 2013
- 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
- Histologically proven intracranial glioblastoma or gliosarcoma with pathologic or radiographic confirmation of tumor progression or regrowth following standard front-line therapy. Patients will be eligible if original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma was made.
- History and physical examination, including neurologic examination and performance status, within 1 week prior to registration
- Systolic blood pressure ≤ 160 mmHg and diastolic pressure ≤ 90 mmHg
- Able to undergo brain magnetic resonance imaging (MRI) scans with intravenous gadolinium
- Radiographic evidence for tumor progression by MRI within 14 days prior to registration
- Karnofsky performance status ≥ 60
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- Complete blood count (CBC)/differential obtained 14 days prior to registration, with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,500/microL; Platelets ≥ 100,000 cells/microL; Hemoglobin ≥ 10.0 gm/dL (use of transfusion or other intervention to achieve Hgb ≥ 10.0 is acceptable)
- Adequate liver function within 14 days prior to registration, defined as follows: serum glutamic oxaloacetic transaminase (SGOT)[aspartic transaminase (AST)]/serum glutamic pyruvic transaminase (SGPT) [alanine transaminase (ALT)] < 2.5 times the upper limit of normal; Bilirubin ≤ 1.6 mg/dL
- Adequate renal function within 14 days prior to registration, defined as: Creatinine ≤ 1.5 mg/dL; Urine protein screened by urine analysis for urine protein creatinine (UPC) ratio. For UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be <1000 mg.
- If not on stable anticoagulation, prothrombin time (PT) must be within normal limits within 14 days prior to registration.
- If on full-dose anticoagulants (e.g., warfarin or LMW heparin) must meet both of the following criteria: No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices); In-range international normalized ratio (INR), usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin.
- Have received prior concurrent and/or adjuvant temozolomide
- Have recovered from toxic effects of prior therapy, and there must be a minimum time of 28 days from the administration of any prior cytotoxicity or investigational agent, except for nitrosureas (>42 days)
- Should not have been previously treated with any other histone deacetylase (HDAC) inhibitors (other than valproic acid for management of seizures). If they have been treated with valproic acid as treatment for seizures, the drug should be stopped at least 30 days before exposure to vorinostat.
- Should not have been previously treated with bevacizumab and/or irinotecan
- Should not have undergone more than 3 prior therapies
- Patients having undergone recent resection of recurrent or progressive tumor must meet all of the following conditions: Patients must have recovered from the effects of surgery and a minimum of 28 days must have elapsed from the day of surgery to the day of registration; If a core or needle biopsy was performed, a minimum of 7 days must have elapsed prior to registration.
- Residual disease following resection of recurrent glioblastoma is not mandated for eligibility into the study.
- Have failed prior radiation therapy and must have an interval of ≥ 42 days (6 weeks) from the completion of initial radiation therapy to registration
- Must sign study-specific informed consent prior to registration
- Women of childbearing potential (WOCBP) must have a negative β-HCG pregnancy test documented within 14 days prior to registration.
- WOCBP must agree to use 2 forms of adequate contraceptive methods. These include (1) oral, injectable, or implantable hormonal contraceptive; (2) tubal ligation; (3) intra-uterine device; (4) barrier contraceptive with spermicide; or (5) vasectomized partner. Men must also protect their partner from becoming pregnant through use of condoms with spermicide or vasectomy. Patient must agree to have standard of care MRIs.
Who cannot join
- Prior invasive malignancy that is not the glioblastoma or gliosarcoma (except nonmelanomatous skin cancer or carcinoma in situ of the cervix) unless patient has been disease free and off therapy for that disease for at least 3 years
- Acute intratumoral hemorrhage on MR imaging. Patients with MR imaging demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) will be eligible for treatment.
- Must not have any 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
- Must not have any severe, active comorbidity, defined as: Transmural myocardial infarction or unstable angina within 6 months prior to study Registration; Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of ≥2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of registration; New York Heart Association (NYHA) grade II or greater or congestive heart failure requiring hospitalization within 12 months prior to registration; history of stroke or transient ischemic attack within 6 months; inadequately controlled hypertension despite antihypertensive medication; serious and inadequately controlled cardiac arrhythmia; significant vascular disease; clinically significant peripheral vascular disease; evidence of bleeding diathesis or coagulopathy; Patients on dialysis; Serious or non-healing wound, ulcer, or bone fracture; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration; acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 14 days prior to registration; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC); cannot be receiving highly active antiretroviral therapy (HAART); must not be diagnosed with hepatitis B or hepatitis C
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration
- Anticipation of need for major surgical procedures during the course of the study
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- Core biopsy within 7 days prior to registration
- Pregnant or nursing breastfeeding should be discontinued prior to enrollment
- Fertile men and women who are sexually active and not willing/able to use medically acceptable forms of contraception during therapy and for at least 6 months after the completion of therapy
- Known hypersensitivity of Chinese hamster ovary cell products or other recombinant human antibodies
- Any condition that impairs ability to swallow pills
- The clearance and metabolism of irinotecan is markedly enhanced in patients receiving drugs that induce the hepatic cytochrome p450 system. In brain tumor patients, these are typically certain types of anticonvulsants, termed enzyme-inducing anti-epileptic drugs (EIAEDs). Patients cannot be receiving EIAEDs or any CYP3A4 inhibitors; patients previously receiving these agents must have discontinued their use at least 2 weeks prior to registration.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, 33612
About this study
Official title: A Phase I Trial of Vorinostat in Combination With Bevacizumab and Irinotecan in Recurrent Glioblastoma
The purpose of the this study is to see if an investigations cancer treatment called vorinostat can be combined with the irinotecan/bevacizumab regimen safely.
Read the detailed description
Drug Administration: (A cycle is 28 days) Irinotecan and bevacizumab are given IV on days 1 and 15 of each cycle. Vorinostat is given orally on days 1-7 and 15-21 of each cycle.
Vorinostat (provided in 100mg capsules) begins at a dose of 200mg/day, escalating to 300mg/day and then to a maximum of 400mg/day. Vorinostat will be taken prior to irinotecan and bevacizumab on days 1 and 15. The drug should be administered at the same time every day for days 2-7 and 16-21. Patients will be treated prophylactically with compazine 30 minutes prior to vorinostat which, in turn, should be taken 30 minutes prior to a meal whenever possible.
Irinotecan is given at a dose of 125mg/m². Bevacizumab is given at a dose of 10mg/kg.
Maximum tolerated dose (MTD) will be defined by toxicities occurring during the first 4 weeks of therapy. Three patients will be treated at dose level one and can be enrolled simultaneously. They must be observed for dose limiting toxicities (DLT) for at least 4 weeks from treatment day 1. Page 15 of the protocol outlines the dose escalation parameters. At least 9 patients will be treated at the MTD. If DLT is not achieved in any cohort of up to a dose level of 400mg/day of vorinostat, further dose escalations will not be made. This dose will then become the recommended dose.
Patients demonstrating evidence of benefit may be treated up to a maximum of 24 cycles, at the investigator's discretion.
- Conditions
- Glioblastoma
- Being tested
- Vorinostat, Bevacizumab, Irinotecan
- Keywords
- recurrent glioblastoma, multiple agents, immunotherapy, chemotherapy, brain and nervous system
- Medical subject headings
- Glioblastoma, Neurologic Manifestations
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VorinostatDrug
Also called NSC 701852
Vorinostat, Bevacizumab and Irinotecan Study. Determine maximum tolerated dose for treatment.
BevacizumabDrug
Also called rhuMAb VEGF, Avastin, NSC 704865
Vorinostat, Bevacizumab and Irinotecan Study. Determine maximum tolerated dose for treatment.
IrinotecanDrug
Also called Camptosar, CPT-11, NSC 616348
Vorinostat, Bevacizumab and Irinotecan Study. Determine maximum tolerated dose for treatment.
| Study group | Role | What they receive |
|---|---|---|
| A - Phase I Dose Escalation | Experimental | Dose Escalation - Irinotecan and bevacizumab are given IV on days 1 and 15 of each cycle. Vorinostat is given orally on days 1-7 and 15-21 of each cycle. Receives: Drug: Vorinostat; Drug: Bevacizumab; Drug: Irinotecan |
| B - Treatment at Maximum Tolerated Dose (MTD) | Experimental | MTD - Treatment at maximum tolerated dose Receives: Drug: Vorinostat; Drug: Bevacizumab; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
Define MTD of vorinostat when combined with bevacizumab and irinotecan
Measured: 25 months
Secondary outcomes (2)
Number of Participants With Progression Free Survival (PFS) at 6 Months
All patients will be evaluable for 6 month-PFS except those that are removed from the study before the end of cycle 1 for reasons other than clinical progression (such as toxicity). Patients who suffer clinical progression without radiographic confirmation of progression will be considered to have progressive disease in determination of 6 month-PFS.
Measured: 6 months
Number of Participants With Adverse Events (AEs)
Characterize characterize the safety profile of vorinostat in combination with bevacizumab and irinotecan. All patients will be evaluable for toxicity from the time of their first treatment.
Measured: 25 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2008 (estimated)
- Study startSep 2008
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Prakash Chinnaiyan, M.D., Principal investigator, H. Lee Moffitt Cancer Center & Research Institute, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00762255
- Sponsor's protocol ID
- MCC-15629
- Other IDs
- 33726
- Status last verified
- Jul 2013
- First submitted
- 29 Sep 2008
- Last updated
- 25 Jul 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Vorinostat in Combination With Bevacizumab and Irinotecan in Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT00762255
- Acronym / sponsor ID
- MCC-15629
- Conditions
- Glioblastoma
- Keywords
- recurrent glioblastoma, multiple agents, immunotherapy, chemotherapy, brain and nervous system
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Sep 2008
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 30 Sep 2008 (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.
The purpose of the this study is to see if an investigations cancer treatment called vorinostat can be combined with the irinotecan/bevacizumab regimen safely.
Detailed description
Drug Administration: (A cycle is 28 days) Irinotecan and bevacizumab are given IV on days 1 and 15 of each cycle. Vorinostat is given orally on days 1-7 and 15-21 of each cycle.
Vorinostat (provided in 100mg capsules) begins at a dose of 200mg/day, escalating to 300mg/day and then to a maximum of 400mg/day. Vorinostat will be taken prior to irinotecan and bevacizumab on days 1 and 15. The drug should be administered at the same time every day for days 2-7 and 16-21. Patients will be treated prophylactically with compazine 30 minutes prior to vorinostat which, in turn, should be taken 30 minutes prior to a meal whenever possible.
Irinotecan is given at a dose of 125mg/m². Bevacizumab is given at a dose of 10mg/kg.
Maximum tolerated dose (MTD) will be defined by toxicities occurring during the first 4 weeks of therapy. Three patients will be treated at dose level one and can be enrolled simultaneously. They must be observed for dose limiting toxicities (DLT) for at least 4 weeks from treatment day 1. Page 15 of the protocol outlines the dose escalation parameters. At least 9 patients will be treated at the MTD. If DLT is not achieved in any cohort of up to a dose level of 400mg/day of vorinostat, further dose escalations will not be made. This dose will then become the recommended dose.
Patients demonstrating evidence of benefit may be treated up to a maximum of 24 cycles, at the investigator's discretion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A - Phase I Dose Escalation | Experimental | Drug: Vorinostat, Drug: Bevacizumab, Drug: IrinotecanDose Escalation - Irinotecan and bevacizumab are given IV on days 1 and 15 of each cycle. Vorinostat is given orally on days 1-7 and 15-21 of each cycle. |
| B - Treatment at Maximum Tolerated Dose (MTD) | Experimental | Drug: Vorinostat, Drug: Bevacizumab, Drug: IrinotecanMTD - Treatment at maximum tolerated dose |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically proven intracranial glioblastoma or gliosarcoma with pathologic or radiographic confirmation of tumor progression or regrowth following standard front-line therapy. Patients will be eligible if original histology was low-grade glioma and a subsequent diagnosis of glioblastoma or gliosarcoma was made.
- History and physical examination, including neurologic examination and performance status, within 1 week prior to registration
- Systolic blood pressure ≤ 160 mmHg and diastolic pressure ≤ 90 mmHg
- Able to undergo brain magnetic resonance imaging (MRI) scans with intravenous gadolinium
- Radiographic evidence for tumor progression by MRI within 14 days prior to registration
Key exclusion criteria (12 listed)
- Prior invasive malignancy that is not the glioblastoma or gliosarcoma (except nonmelanomatous skin cancer or carcinoma in situ of the cervix) unless patient has been disease free and off therapy for that disease for at least 3 years
- Acute intratumoral hemorrhage on MR imaging. Patients with MR imaging demonstrating old hemorrhage or subacute blood after a neurosurgical procedure (biopsy or resection) will be eligible for treatment.
- Must not have any 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
- Must not have any severe, active comorbidity, defined as: Transmural myocardial infarction or unstable angina within 6 months prior to study Registration; Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of ≥2 mm using the analysis of an electrocardiogram (EKG) performed within 14 days of registration; New York Heart Association (NYHA) grade II or greater or congestive heart failure requiring hospitalization within 12 months prior to registration; history of stroke or transient ischemic attack within 6 months; inadequately controlled hypertension despite antihypertensive medication; serious and inadequately controlled cardiac arrhythmia; significant vascular disease; clinically significant peripheral vascular disease; evidence of bleeding diathesis or coagulopathy; Patients on dialysis; Serious or non-healing wound, ulcer, or bone fracture; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to registration; acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration; chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 14 days prior to registration; acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC); cannot be receiving highly active antiretroviral therapy (HAART); must not be diagnosed with hepatitis B or hepatitis C
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration
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: NSC 701852Vorinostat, Bevacizumab and Irinotecan Study. Determine maximum tolerated dose for treatment. | Drug | A - Phase I Dose Escalation, B - Treatment at Maximum Tolerated Dose (MTD) |
| BevacizumabAlso: rhuMAb VEGF, Avastin, NSC 704865Vorinostat, Bevacizumab and Irinotecan Study. Determine maximum tolerated dose for treatment. | Drug | A - Phase I Dose Escalation, B - Treatment at Maximum Tolerated Dose (MTD) |
| IrinotecanAlso: Camptosar, CPT-11, NSC 616348Vorinostat, Bevacizumab and Irinotecan Study. Determine maximum tolerated dose for treatment. | Drug | A - Phase I Dose Escalation, B - Treatment at Maximum Tolerated Dose (MTD) |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 25 months
Define MTD of vorinostat when combined with bevacizumab and irinotecan
2 secondary outcomes
Number of Participants With Progression Free Survival (PFS) at 6 Months
Time frame: 6 months
Number of Participants With Adverse Events (AEs)
Time frame: 25 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 25 Jul 2013.
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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.
Prakash Chinnaiyan, M.D. principal investigator
H. Lee Moffitt Cancer Center & Research Institute, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vorinostat, Bevacizumab and Irinotecan in people with Glioblastoma, run by H. Lee Moffitt Cancer Center and Research Institute 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 22 inclusion and 12 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 25 Jul 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 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?
Maximum Tolerated Dose (MTD) (time frame: 25 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 25 Jul 2013.