Primary Glioblastoma MultiformePhase 2TemodarNCT00574964
Gliadel Wafers and Temodar in the Treatment of Glioblastoma Multiforme
A Phase 2 study testing Gliadel Wafer, Temodar and Radiotherapy in people with Primary Glioblastoma Multiforme, run by University of Iowa at 1 site in United States.
Trial summary
The purpose of this research study is to determine if combining all three treatments of Gliadel wafers, Temozolomide and Radiation therapy at the same time is safe and more effective than one treatment at a time. The study will measure the survival of subjects treated with this combination of drugs. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Primary Glioblastoma Multiforme
- What is being tested?
- Gliadel Wafer, Temodar and Radiotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Jun 2008
- Phase
- Phase 2
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to understand and the willingness to sign a written informed consent document.
- Subjects must have findings on neuroimaging studies and clinical evaluation consistent with the diagnosis of a primary brain tumor in order to be offered enrollment in the study. Subsequently, in order to remain on study, they must have histologically or cytologically confirmed primary tumor of the brain. Intra-operative confirmation of histology (i.e. frozen section assessment or equivalent) is required for all subjects. Gliadel wafers will not be implanted without positive intraoperative histopathology consistent with a primary tumor of the brain. The final classification and evaluability determination will be made based on post-operative histological reports showing anaplastic astrocytoma or Glioblastoma multiforme. No central pathology review will be required.
- Newly diagnosed supratentorial primary brain lesion as visualized on enhanced MRI scan (or CT scan with contrast for subjects who cannot undergo MRI) that is appropriate for surgical resection and implantation of Gliadel.
- All eligible subjects will undergo surgical resection. After resection, if there is communication of the resection cavity with the ventricular spaces preventing the use of Gliadel® the subject leaves the study.
- MRI or CT with and without contrast within 30 days of study entry.
- New diagnosis of primary brain tumor is required. No prior therapy, including previous radiotherapy, chemotherapy, or operation is allowed.
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- Age 18 years and older, since the rationale for this therapy was established in adults, and the tumor uncommon in children, so that no useful information is likely to emerge from their inclusion in this study.
- Karnofsky Performance Status greater than or equal to 60.
- Life expectancy of at least 12 weeks.
- Subjects must have normal organ and marrow function as defined below:
- WBC greater than or equal 2,000/mm3
- Absolute neutrophil count greater than or equal to 1,500/mm3
- Platelets greater than or equal to 125,000/mm3
- Total bilirubin less than or equal to 2.0 mg/dl
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X upper limit of normal
- PT / PTT within 1.5 X upper limit of normal
- Creatinine less than or equal to 1.7 mg/dl
- BUN less than or equal to 40 mg/dl
- Hemoglobin > 10 g/dL
- Clinical evaluation of cardiac and pulmonary functions consistent with adequate tolerance of surgical procedure.
- Negative pregnancy test (beta HCG) if a female of childbearing age and not surgically sterilized.
- The effects of BCNU (the active ingredient in the Gliadel wafer) with concomitant Temozolomide on the developing human fetus are unknown. BCNU is known to cause fetal harm if administered to a pregnant woman and is a pregnancy risk factor D. Temozolomide May cause fetal harm when administered to pregnant women. Animal studies, at doses less than used in humans, resulted in numerous birth defects. Testicular toxicity was demonstrated in animal studies using smaller doses than recommended for cancer treatment. Temozolomide is also a pregnancy risk factor D. Radiation therapy is known to be both mutagenic and teratogenic. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, or if her partner is participating in this trial, she should inform the treating physician immediately.
Who cannot join
- Known hypersensitivity or allergy to BCNU (carmustine) or other components of the Gliadel® wafer such as polifeprosan polymer.
- Known hypersensitivity to temozolomide.
- Subjects may not be receiving any other investigational agents.
- If the surgeon determines that placement of Gliadel wafers is inappropriate, or if the final diagnosis is other than anaplastic astrocytoma or glioblastoma, the subject will leave the study and not be further analyzed.
- Subjects who have had chemotherapy or radiotherapy at any time for this diagnosis.
- A subject will be considered unresectable preoperatively if, in the opinion of the neurosurgeon, the subject is not a candidate for maximal cytoreductive surgery, (i.e., crosses the midline, continuous with the ventricular space). Such subjects will not be eligible for treatment on this protocol.
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- Diagnosis of prior central nervous system tumor.
- Diagnosis of systemic cancer requiring treatment within the past five years (except for non-melanotic carcinoma of the skin or carcinoma in situ of the cervix).
- Open communication of the resection cavity with the ventricular system that prevents insertion of Gliadel or tumors that cross the midline.
- Posterior fossa or brain stem tumor.
- Concurrent severe medical illness (e.g., active infection, acute hepatitis, cardiac arrhythmia, unstable angina, congestive heart failure, uncontrolled diabetes mellitus, uncontrolled seizures, pulmonary insufficiency, pulmonary fibrosis, pulmonary embolus, etc) or psychiatric illness, or abnormal laboratory values that preclude surgical candidacy or limits expected survival to less than 12 weeks.
- Pregnant women are excluded from this study because BCNU and/or Temozolomide are pregnancy risk D pharmaceutical agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with BCNU and/or Temozolomide, breastfeeding should be discontinued if the mother is treated with either of these agents. These potential risks may also apply to other agents used in this study.
- Subjects with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. Therefore, HIV-positive subjects receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with BCNU or other agents administered during the study. Appropriate studies will be undertaken in subjects receiving combination anti-retroviral therapy when indicated.
Trial locations and contacts
1 site in 1 country.
United States1 site
Holden Comprehensive Cancer Clinic
Iowa City, Iowa, 52242
About this study
Official title: Phase II Treatment of Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme Treated With Gliadel Wafers, Surgery and Limited Field Radiation Plus Concomitant Temozolomide Followed by Temozolomide
The purpose of this research study is to determine if combining all three treatments of Gliadel wafers, Temozolomide and Radiation therapy at the same time is safe and more effective than one treatment at a time. The study will measure the survival of subjects treated with this combination of drugs.
Read the detailed description
Subjects will receive surgery + Gliadel® wafer implantation + Limited Field Radiation Therapy to a dose of 61.2 Gy with concomitant daily temozolomide. Up to 8 wafers will be implanted into the tumor resection cavity (depending upon its size) after maximal tumor resection. Between days 10 and 30 all subjects will begin a standard course of post-operative limited field radiation therapy to the tumor site and a surrounding margin, with concomitant daily temozolomide (75mg/m2 x 7 d/wk for 6 weeks, concomitant chemoradiotherapy phase). Beginning no later than 45 days following completion of radiation, temozolomide will be given at a dosage of 200 mg/m2 daily for five days on a 28 day schedule, for a total of 6 cycles (adjuvant chemotherapy phase). Subjects will be monitored weekly during chemoradiotherapy with CBC with differential and brief clinical assessment, and monthly during the adjuvant chemotherapy phase. Toxicity reports will be assessed every three months. Dose limiting toxicities (DLT) are defined in section 4.2. If toxic events unresponsive to planned dose modification exceed 20% of enrolled subjects the stopping rule will be met and the study will be discontinued. MRIs will be obtained no more than 72 hours post-op, and then prior to the first, third, and fifth cycles of monthly temozolomide. Additionally, a stealth MRI or CT scan (with or without contrast) will be done one week prior to radiotherapy for treatment planning at the discretion of the treating Radiation Oncologist. Following completion of the entire course of treatment subjects will be monitored clinically as well as with MRI every 3 months for survival and evidence of progression.
- Conditions
- Primary Glioblastoma Multiforme
- Being tested
- Gliadel Wafer, Temodar and Radiotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gliadel Wafer, Temodar and RadiotherapyOther
Given concurrently starting 10-30 days after surgery.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Other: Gliadel Wafer, Temodar and Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the safety and feasibility of Gliadel 3.85% wafers plus surgery and limited field radiation therapy with concomitant temozolomide, followed by adjuvant temozolomide, in subjects undergoing initial surgery for newly-diagnosed malignant gliomas.
Measured: Will follow subjects to collect DOD.
Secondary outcomes (1)
Determine the progression free survival at 6 months, medial survival, and one year survival rate of this subject population. Determine objective response rate.
Measured: Will follow subject to collect DOD.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2007 (estimated)
- Study startOct 2005
- Primary completionNov 2007
- Study completionJun 2008
Why it stopped: PI left the institution.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by University of IowaThe 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
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Investigators
- Timothy Ryken, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00574964
- Sponsor's protocol ID
- 200408035
- Acronym
- Temodar
- Status last verified
- Mar 2010
- First submitted
- 14 Dec 2007
- Last updated
- 27 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Treatment of Adults With Newly Diagnosed Supratentorial Glioblastoma Multiforme Treated With Gliadel Wafers, Surgery and Limited Field Radiation Plus Concomitant Temozolomide Followed by Temozolomide
- ClinicalTrials.gov ID
- NCT00574964
- Acronym / sponsor ID
- Temodar / 200408035
- Conditions
- Primary Glioblastoma Multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left the institution.
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- Oct 2005
- Primary completion
- Nov 2007 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 17 Dec 2007 (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 this research study is to determine if combining all three treatments of Gliadel wafers, Temozolomide and Radiation therapy at the same time is safe and more effective than one treatment at a time. The study will measure the survival of subjects treated with this combination of drugs.
Detailed description
Subjects will receive surgery + Gliadel® wafer implantation + Limited Field Radiation Therapy to a dose of 61.2 Gy with concomitant daily temozolomide. Up to 8 wafers will be implanted into the tumor resection cavity (depending upon its size) after maximal tumor resection. Between days 10 and 30 all subjects will begin a standard course of post-operative limited field radiation therapy to the tumor site and a surrounding margin, with concomitant daily temozolomide (75mg/m2 x 7 d/wk for 6 weeks, concomitant chemoradiotherapy phase). Beginning no later than 45 days following completion of radiation, temozolomide will be given at a dosage of 200 mg/m2 daily for five days on a 28 day schedule, for a total of 6 cycles (adjuvant chemotherapy phase). Subjects will be monitored weekly during chemoradiotherapy with CBC with differential and brief clinical assessment, and monthly during the adjuvant chemotherapy phase. Toxicity reports will be assessed every three months. Dose limiting toxicities (DLT) are defined in section 4.2. If toxic events unresponsive to planned dose modification exceed 20% of enrolled subjects the stopping rule will be met and the study will be discontinued. MRIs will be obtained no more than 72 hours post-op, and then prior to the first, third, and fifth cycles of monthly temozolomide. Additionally, a stealth MRI or CT scan (with or without contrast) will be done one week prior to radiotherapy for treatment planning at the discretion of the treating Radiation Oncologist. Following completion of the entire course of treatment subjects will be monitored clinically as well as with MRI every 3 months for survival and evidence of progression.
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 | Other: Gliadel Wafer, Temodar and Radiotherapy |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Ability to understand and the willingness to sign a written informed consent document.
- Subjects must have findings on neuroimaging studies and clinical evaluation consistent with the diagnosis of a primary brain tumor in order to be offered enrollment in the study. Subsequently, in order to remain on study, they must have histologically or cytologically confirmed primary tumor of the brain. Intra-operative confirmation of histology (i.e. frozen section assessment or equivalent) is required for all subjects. Gliadel wafers will not be implanted without positive intraoperative histopathology consistent with a primary tumor of the brain. The final classification and evaluability determination will be made based on post-operative histological reports showing anaplastic astrocytoma or Glioblastoma multiforme. No central pathology review will be required.
- Newly diagnosed supratentorial primary brain lesion as visualized on enhanced MRI scan (or CT scan with contrast for subjects who cannot undergo MRI) that is appropriate for surgical resection and implantation of Gliadel.
- All eligible subjects will undergo surgical resection. After resection, if there is communication of the resection cavity with the ventricular spaces preventing the use of Gliadel® the subject leaves the study.
- MRI or CT with and without contrast within 30 days of study entry.
Key exclusion criteria (13 listed)
- Known hypersensitivity or allergy to BCNU (carmustine) or other components of the Gliadel® wafer such as polifeprosan polymer.
- Known hypersensitivity to temozolomide.
- Subjects may not be receiving any other investigational agents.
- If the surgeon determines that placement of Gliadel wafers is inappropriate, or if the final diagnosis is other than anaplastic astrocytoma or glioblastoma, the subject will leave the study and not be further analyzed.
- Subjects who have had chemotherapy or radiotherapy at any time for this diagnosis.
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 Wafer, Temodar and RadiotherapyGiven concurrently starting 10-30 days after surgery. | Other | 1 |
Primary outcome
Determine the safety and feasibility of Gliadel 3.85% wafers plus surgery and limited field radiation therapy with concomitant temozolomide, followed by adjuvant temozolomide, in subjects undergoing initial surgery for newly-diagnosed malignant gliomas.
Time frame: Will follow subjects to collect DOD.
1 secondary outcome
Determine the progression free survival at 6 months, medial survival, and one year survival rate of this subject population. Determine objective response rate.
Time frame: Will follow subject to collect DOD.
Results and safety
The study was stopped early (reason given: PI left the institution.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 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.
Timothy Ryken, MD principal investigator
University of Iowa
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 Wafer, Temodar and Radiotherapy in people with Primary Glioblastoma Multiforme, run by University of Iowa 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 13 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 27 Oct 2016. 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?
The study was stopped early (reason given: PI left the institution.). Results are not available in the source record.
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?
Determine the safety and feasibility of Gliadel 3.85% wafers plus surgery and limited field radiation therapy with concomitant temozolomide, followed by adjuvant temozolomide, in subjects undergoing initial surgery for newly-diagnosed malignant gliomas. (time frame: Will follow subjects to collect DOD.). 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 Oct 2016.