Malignant GliomaPhase 2NCT00735436
A Study of Gliadel Followed by Avastin + Irinotecan for Glioblastoma Multiforme (GBM)
A Phase 2 study testing Gliadel/Avastin/CPT-11 in people with Malignant Glioma and Glioblastoma Multiforme, run by Duke University at 1 site in United States.
Trial summary
The primary objective of the study is to use 24 week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Glioblastoma Multiforme, Gliosarcoma
- What is being tested?
- Gliadel/Avastin/CPT-11
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Oct 2012
- 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
- Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be able to undergo a GTR.
- Age > or = 18 years
- Evidence of a unilateral, single focus of measurable central nervous system (CNS) neoplasm on contrast-enhanced MRI, unless medically contraindicated (CT scan will then be used)
- Patients must have < or = 2 disease progressions
- An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol
- Karnofsky > or = 70%
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- Hemoglobin > or = 9.0 g/dl, absolute neutrophil count (ANC) > or = 1,500 cells/microliters, platelets > or = 125,000 cells/microliters
- Serum creatinine < or = 1.5 mg/dl, serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin < or = 1.5 times upper limit of normal
- Patients on corticosteroids must have been on a stable dose for 1 week prior to entry, if clinically possible, and the dose should not be escalated over entry dose level
- If patient received chemotherapy or investigational agent as part of their prior therapy, the patient must recover from all toxicities (> or = Grade 1) prior to enrollment on this protocol
- Signed informed consent approved by the Institutional Review Board
- No evidence of CNS hemorrhage on the baseline MRI or CT scans
- If sexually active, patients will take contraceptive measures for the duration of treatment as stated in the informed consent
Who cannot join
- Pregnancy or breast feeding. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to treatment administration
- Multifocal disease
- Prior treatment with Gliadel
- Prior treatment with CPT-11 or Avastin
- Prior stereotactic radiosurgery or brachytherapy
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
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- Active infection requiring IV antibiotics
- Acute or chronic renal insufficiency (a glomerular filtration rate (GFR) <30 mL/min/1.73m2) or acute renal insufficiency of any severity due to hepato-renal syndrome or in the peri-operative liver transplantation period
- Inability, in the opinion of the study investigator, to comply with study and/or follow-up procedures
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
- Life expectancy of less than 12 weeks
- Active malignancy, other than superficial basal cell and superficial squamous (skin) cell, or carcinoma in situ of the cervix within last five years
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day 1
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- History of hemoptysis (> or = 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- History of abdominal fistula, gastrointestinal perforation within 6 months prior to Day 1
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Proteinuria at screening as demonstrated by urinalysis (urine protein)
- Known hypersensitivity to any component of Avastin
- Pregnancy (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
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 II Trial for Patients With Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Avastin Plus Irinotecan
The primary objective of the study is to use 24 week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. The secondary objectives are to determine the progression-free survival following the combination of Gliadel followed by Avastin and irinotecan and to describe the toxicity of Gliadel followed by Avastin and irinotecan.
Read the detailed description
This is a phase II study of the combination of Gliadel followed by Avastin and irinotecan in grade IV malignant glioma patients. The study will have survival and toxicity endpoints. Subjects will be identified by the investigator as those patients who have histologically documented grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with recurrent or progressive disease who are able to undergo a gross total resection (GTR).
Part I: Gliadel wafer- 1-8 wafers inserted at time of gross total resection. Treatment cycle is 42 days in length. For patients with ≥ Grade 1 toxicity will allow 84 days prior to beginning therapy with Avastin and Irinotecan (CPT-11).
Part II: Avastin Plus Irinotecan (Cycles 1-12) consists of the following (cycle length is 6 weeks):
- Irinotecan 125 mg/m2 (not taking enzyme-inducing anti-epileptic drugs (EIAEDs)) or 340 mg/m2 (taking EIAEDs) given every two weeks on days 1, 15, 29, etc.;
- If the patient has the uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction; For patients on an EIAED, the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2;
- Avastin 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29, etc.
The primary objective of this phase II study is to determine whether the administration of Gliadel wafers followed by Avastin and irinotecan to patients with recurrent GBM is a treatment regimen worthy of further investigation in a randomized clinical trial. The basis for making this decision will be the proportion of patients who survive at least 24 weeks after initiation of protocol treatment.
In the initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The two major toxicities associated with irinotecan are myelosuppression and diarrhea. Side effects associated with Gliadel are seizures, brain edema (swelling), healing abnormalities, wound infection and body pain.
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, Gliosarcoma
- Being tested
- Gliadel/Avastin/CPT-11
- Keywords
- Malignant glioma, Glioblastoma multiforme, GBM, Gliosarcoma, Gliadel, Carmustine, Irinotecan, CPT-11, Camptosar, Avastin, Bevacizumab
- Medical subject headings
- Glioma, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gliadel/Avastin/CPT-11Drug
Also called bevacizumab, irinotecan
| Study group | Role | What they receive |
|---|---|---|
| Gliadel/Avastin/CPT-11 | Other | Gliadel/Avastin/CPT-11 Receives: Drug: Gliadel/Avastin/CPT-11 |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-week Overall Survival
The percentage of participants surviving 24 weeks from the start of study treatment
Measured: 24 weeks
Secondary outcomes (5)
24-week Progression-free Survival (PFS)
The percentage of participants surviving 24 weeks 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 modified Macdonald criteria, or to death due to any cause.
Measured: 24 weeks
Median Progression-free Survival (PFS)
Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria, or to death due to any cause. 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: Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 47 months
Median Overall Survival (OS)
Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Measured: Time in months from the start of study treatment to date of death due to any cause, assessed up to 47 months
Incidence and Severity of Central Nervous System (CNS) Hemorrhage
Incidence and severity of CNS hemorrhage
Measured: 47 months
Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities
Incidence of grade ≥ 4 hematologic and ≥ grade 3 non-hematologic toxicities
Measured: 47 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2008 (estimated)
- Study startDec 2008
- Primary completionJul 2011
- Study completionOct 2012
Why it stopped: Study enrollment was halted due to slow accrual.
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 Malignant GliomaStudies of the same condition, open and under way.
- More trials run by Duke 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc., Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Annick Desjardins, MD, FRCPC, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00735436
- Sponsor's protocol ID
- Pro00006308
- Status last verified
- Dec 2012
- First submitted
- 13 Aug 2008
- Last updated
- 11 Feb 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 11 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial for Patients With Glioblastoma Multiforme (GBM) Treated With Gliadel Followed by Avastin Plus Irinotecan
- ClinicalTrials.gov ID
- NCT00735436
- Acronym / sponsor ID
- Pro00006308
- Conditions
- Malignant Glioma, Glioblastoma Multiforme, Gliosarcoma
- Keywords
- Malignant glioma, Glioblastoma multiforme, GBM, Gliosarcoma, Gliadel, Carmustine, Irinotecan, CPT-11
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study enrollment was halted due to slow accrual.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Eisai Inc., Genentech, Inc.
- Study start
- Dec 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 15 Aug 2008 (estimated)
- Results
- Posted 4 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of the study is to use 24 week survival to assess the efficacy of the combination of Gliadel followed by Avastin and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. The secondary objectives are to determine the progression-free survival following the combination of Gliadel followed by Avastin and irinotecan and to describe the toxicity of Gliadel followed by Avastin and irinotecan.
Detailed description
This is a phase II study of the combination of Gliadel followed by Avastin and irinotecan in grade IV malignant glioma patients. The study will have survival and toxicity endpoints. Subjects will be identified by the investigator as those patients who have histologically documented grade IV malignant glioma (glioblastoma multiforme or gliosarcoma) with recurrent or progressive disease who are able to undergo a gross total resection (GTR).
Part I: Gliadel wafer- 1-8 wafers inserted at time of gross total resection. Treatment cycle is 42 days in length. For patients with ≥ Grade 1 toxicity will allow 84 days prior to beginning therapy with Avastin and Irinotecan (CPT-11).
Part II: Avastin Plus Irinotecan (Cycles 1-12) consists of the following (cycle length is 6 weeks):
- Irinotecan 125 mg/m2 (not taking enzyme-inducing anti-epileptic drugs (EIAEDs)) or 340 mg/m2 (taking EIAEDs) given every two weeks on days 1, 15, 29, etc.;
- If the patient has the uridine diphosphate (UDP) glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) polymorphism (7/7), they do not metabolize the irinotecan normally, so these patients will start out at a two dose level reduction; For patients on an EIAED, the starting dose will be 275 mg/M2, and for patients not on an EIAED, the starting dose will be 75 mg/M2;
- Avastin 10 mg/kg immediately after the irinotecan given every 2 weeks on days 1, 15, 29, etc.
The primary objective of this phase II study is to determine whether the administration of Gliadel wafers followed by Avastin and irinotecan to patients with recurrent GBM is a treatment regimen worthy of further investigation in a randomized clinical trial. The basis for making this decision will be the proportion of patients who survive at least 24 weeks after initiation of protocol treatment.
In the initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. The two major toxicities associated with irinotecan are myelosuppression and diarrhea. Side effects associated with Gliadel are seizures, brain edema (swelling), healing abnormalities, wound infection and body pain.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gliadel/Avastin/CPT-11 | Other | Drug: Gliadel/Avastin/CPT-11Gliadel/Avastin/CPT-11 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be able to undergo a GTR.
- Age > or = 18 years
- Evidence of a unilateral, single focus of measurable central nervous system (CNS) neoplasm on contrast-enhanced MRI, unless medically contraindicated (CT scan will then be used)
- Patients must have < or = 2 disease progressions
- An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol
Key exclusion criteria (27 listed)
- Pregnancy or breast feeding. Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to treatment administration
- Multifocal disease
- Prior treatment with Gliadel
- Prior treatment with CPT-11 or Avastin
- Prior stereotactic radiosurgery or brachytherapy
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 |
|---|---|---|
| Gliadel/Avastin/CPT-11Also: bevacizumab, irinotecan | Drug | Gliadel/Avastin/CPT-11 |
Primary outcome
24-week Overall Survival
Time frame: 24 weeks
The percentage of participants surviving 24 weeks from the start of study treatment
5 secondary outcomes
24-week Progression-free Survival (PFS)
Time frame: 24 weeks
Median Progression-free Survival (PFS)
Time frame: Time in months from the start of study treatment to the date of first progression according to modified Macdonald criteria or to death due to any cause, assessed up to 47 months
Median Overall Survival (OS)
Time frame: Time in months from the start of study treatment to date of death due to any cause, assessed up to 47 months
Incidence and Severity of Central Nervous System (CNS) Hemorrhage
Time frame: 47 months
Incidence of Grade ≥ 4 Hematologic and ≥ Grade 3 Non-hematologic Toxicities
Time frame: 47 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Duke University Medical Center Clinical TrialsLink provided by the sponsor.
- The Preston Robert Tisch Brain Tumor CenterLink provided by the sponsor.
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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.
Annick Desjardins, MD, FRCPC 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 2 study testing Gliadel/Avastin/CPT-11 in people with Malignant Glioma and Glioblastoma Multiforme, run by Duke University 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 13 inclusion and 27 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: stopped early, as of the sponsor's last update on 11 Feb 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 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 4 Feb 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?
24-week Overall Survival (time frame: 24 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 11 Feb 2013.