GlioblastomaPhase 1NCT00612638
Ph. I Temozolomide + O6-BG + Irinotecan in Treatment of Pts w Recurrent / Progressive Cerebral Anaplastic Gliomas
A Phase 1 study testing Temodar, O6-BG, and Irinotecan in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site in United States.
Trial summary
Objectives: To determine maximum tolerated dose of CPT-11 when administered following Temodar plus O6-benzylguanine To characterize any toxicity associated w combo of CPT-11 + Temodar plus O6-BG To observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar + O6-BG Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Temodar, O6-BG, 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
- 96 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2005to Jul 2008
- 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
- Pts have histologically confirmed diagnosis of recurrent primary malignant glioma
- Age >18yrs
- Evidence of measurable recurrent/residual primary CNS neoplasm on contrast-enhanced MRI, unless medically contraindicated
- An interval of >2 wks between prior surgical resection/6 wks between prior XRT/chemo, \& enrollment on protocol, unless there is unequivocal evidence of tumor progression after surgery, XRT/chemo
- KPS>60 percent
- Adequate hematologic, renal \& liver function as demonstrated by lab values performed within 14 days, inclusive, prior to administration of chemo:
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- ANC >1500/mm3
- Platelet count > 00,000/mm3
- Hemoglobin > 10gm/dL
- BUN \& serum creatinine <1.5 x ULN
- Total serum bilirubin <1.5 x ULN
- SGOT \& SGPT < 2.5 x ULN
- Alkaline phosphatase of< 2 x ULN
- Pts must have recovered from any effects of major surgery.=
- Pts must have life expectancy of >12wks
- Pts/legal guardian must give written, informed consent
Who cannot join
- Pts requiring immediate XRT
- Pts have not recovered from surgery
- Pts are not neurologically stable for 2wks prior to study entry
- Pts are poor medical risks because of non-malignant systemic disease as well as those w acute infection treated w intravenous antibiotics
- Frequent vomiting/medical condition that could interfere w oral medication intake
- Previous active malignancy treated in past year except for localized in-situ carcinomas \& basal/squamous cell carcinoma of skin
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- Known HIV positivity/AIDS-related illness
- Pregnant/nursing women
- Women of childbearing potential who are not using effective method of contraception. Women of childbearing potential must have negative serum pregnancy test 24 hrs prior to administration of study drug \& be practicing medically approved contraceptive precautions
- Men who are not advised to use effective method of contraception
- Prior failure of CPT-11
- Pts taking immuno-suppressive agents other than prescribed corticosteroids
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Phase I Trail of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) Plus Irinotecan (CPT-11) (NSC 616348) in the Treatment of Patients With Recurrent / Progressive Cerebral Anaplastic Gliomas
Objectives:
To determine maximum tolerated dose of CPT-11 when administered following Temodar plus O6-benzylguanine To characterize any toxicity associated w combo of CPT-11 + Temodar plus O6-BG To observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar + O6-BG
Read the detailed description
Objectives of study: to determine maximum tolerated dose of CPT-11 when administered following Temodar + O6-benzylguanine (O6-BG); to characterize any toxicity associated w combo of CPT-11 + Temodar + O6-BG; to observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar plus O6-BG. Pts have histologically confirmed diagnosis of recurrent primary malignant glioma. 2 separate strata accrued independently of each other: Stratum 1-pts receiving Dilantin, Tegretol/phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. Each strata will be treated \& escalated independent of each other.
Pre-chemo, O6-BG administered intravenously at 120 mg/m2, over 1hr, prior to administration of Temodar on day 1 of 21-day cycle. Post-chemo, O6-BG administered intravenously at 30 mg/m2/day, over 48hrs, immediately after completion of the CPT-11 infusion on day 1 of 21-day cycle. Temodar administered orally at 355 mg/m2, in fasting state, within 60 minutes of the end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3 weeks following dose of Temozolomide from previous cycle. CPT-11 will be administered intravenously in fasting state over 90min. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60 mg/m2 for stratum 1 \& 40 mg/m2 for stratum 2. Treatment cycles may be repeated every 3 wks following dose of CPT-11 from previous cycle.
Major toxicities associated w CPT- 11 are myelosuppression \& diarrhea. Temozolomide has been well tolerated by both adults \& children w most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea \& vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, \& hepatotoxicity. Hypersensitivity reactions have not yet been noted w Temozolomide. As is case w many anti-cancer drugs, Temozolomide may be carcinogenic. O6-BG toxicities include transient lymphopenia has been seen w O6-BG as single agent. O6-BG in combo w other agents could cause exacerbation of any adverse event currently known to be caused by other agent,/ combo may result in events never previously associated w either agent. Animal studies indicated that agitation, lethargy, convulsions, nausea, vomiting, rapid heart rate, elevated liver functions, leukopenia, lymphopenia could be seen.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Temodar, O6-BG, and Irinotecan
- Keywords
- Temodar, Temozolomide, O6-Benzylguanine, O6-BG, NSC 637037, Irinotecan, CPT-11, Recurrent cerebral anaplastic glioma, Progressive cerebral anaplastic glioma, Malignant glioma
- Medical subject headings
- Glioblastoma, Gliosarcoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temodar, O6-BG, and IrinotecanDrug
Also called Temodar-Temozolomide, O6-Benzylguanine-O6-BG, Irinotecan-Camptosar-CPT 11
2 separate strata accrued independently: Stratum 1-pts receiving Dilantin, Tegretol or phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. O6-BG administered intravenously 120mg/m2, over 1hr, prior to administration of Temozolomide on day 1 of 21day cycle. O6-BG administered intravenously 30mg/m2/day, over 48hrs, immediately after completion of CPT-11 infusion on day 1 of 21-day cycle. Temozolomide administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temozolomide from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60mg/m2 for stratum 1 \& 40mg/m2 for stratum2. Treatment cycles repeated every 3 wks following dose of CPT-11 from previous cycle.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Pts receiving Dilantin, Tegretol or Phenobarbital Receives: Drug: Temodar, O6-BG, and Irinotecan |
| 2 | Experimental | Pts on anti-convulsants other than Dilantin, Tegretol / Phenobarbital / pts not on any anti-convulsants Receives: Drug: Temodar, O6-BG, and Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of toxicities
Measured: 6 months
Secondary outcomes (1)
Response rate & progression-free survival
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study startJan 2005
- Primary completionJan 2007
- Study completionJul 2008
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 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Keryx / AOI Pharmaceuticals, Inc., Pharmacia
- Investigators
- David A. Reardon, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612638
- Sponsor's protocol ID
- Pro00007681
- Status last verified
- Jan 2009
- First submitted
- 29 Jan 2008
- Last updated
- 19 Jun 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trail of Temodar Plus O6-Benzylguanine (O6-BG) (NSC 637037) Plus Irinotecan (CPT-11) (NSC 616348) in the Treatment of Patients With Recurrent / Progressive Cerebral Anaplastic Gliomas
- ClinicalTrials.gov ID
- NCT00612638
- Acronym / sponsor ID
- Pro00007681
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Temodar, Temozolomide, O6-Benzylguanine, O6-BG, NSC 637037, Irinotecan, CPT-11, Recurrent cerebral anaplastic glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Keryx / AOI Pharmaceuticals, Inc., Pharmacia
- Study start
- Jan 2005
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 12 Feb 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.
Objectives:
To determine maximum tolerated dose of CPT-11 when administered following Temodar plus O6-benzylguanine To characterize any toxicity associated w combo of CPT-11 + Temodar plus O6-BG To observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar + O6-BG
Detailed description
Objectives of study: to determine maximum tolerated dose of CPT-11 when administered following Temodar + O6-benzylguanine (O6-BG); to characterize any toxicity associated w combo of CPT-11 + Temodar + O6-BG; to observe pts for clinical antitumor response when treated w combo of CPT-11 + Temodar plus O6-BG. Pts have histologically confirmed diagnosis of recurrent primary malignant glioma. 2 separate strata accrued independently of each other: Stratum 1-pts receiving Dilantin, Tegretol/phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. Each strata will be treated \& escalated independent of each other.
Pre-chemo, O6-BG administered intravenously at 120 mg/m2, over 1hr, prior to administration of Temodar on day 1 of 21-day cycle. Post-chemo, O6-BG administered intravenously at 30 mg/m2/day, over 48hrs, immediately after completion of the CPT-11 infusion on day 1 of 21-day cycle. Temodar administered orally at 355 mg/m2, in fasting state, within 60 minutes of the end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3 weeks following dose of Temozolomide from previous cycle. CPT-11 will be administered intravenously in fasting state over 90min. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60 mg/m2 for stratum 1 \& 40 mg/m2 for stratum 2. Treatment cycles may be repeated every 3 wks following dose of CPT-11 from previous cycle.
Major toxicities associated w CPT- 11 are myelosuppression \& diarrhea. Temozolomide has been well tolerated by both adults \& children w most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea \& vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, \& hepatotoxicity. Hypersensitivity reactions have not yet been noted w Temozolomide. As is case w many anti-cancer drugs, Temozolomide may be carcinogenic. O6-BG toxicities include transient lymphopenia has been seen w O6-BG as single agent. O6-BG in combo w other agents could cause exacerbation of any adverse event currently known to be caused by other agent,/ combo may result in events never previously associated w either agent. Animal studies indicated that agitation, lethargy, convulsions, nausea, vomiting, rapid heart rate, elevated liver functions, leukopenia, lymphopenia could be seen.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Temodar, O6-BG, and IrinotecanPts receiving Dilantin, Tegretol or Phenobarbital |
| 2 | Experimental | Drug: Temodar, O6-BG, and IrinotecanPts on anti-convulsants other than Dilantin, Tegretol / Phenobarbital / pts not on any anti-convulsants |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Pts have histologically confirmed diagnosis of recurrent primary malignant glioma
- Age >18yrs
- Evidence of measurable recurrent/residual primary CNS neoplasm on contrast-enhanced MRI, unless medically contraindicated
- An interval of >2 wks between prior surgical resection/6 wks between prior XRT/chemo, \& enrollment on protocol, unless there is unequivocal evidence of tumor progression after surgery, XRT/chemo
- KPS>60 percent
Key exclusion criteria (12 listed)
- Pts requiring immediate XRT
- Pts have not recovered from surgery
- Pts are not neurologically stable for 2wks prior to study entry
- Pts are poor medical risks because of non-malignant systemic disease as well as those w acute infection treated w intravenous antibiotics
- Frequent vomiting/medical condition that could interfere w oral medication intake
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 |
|---|---|---|
| Temodar, O6-BG, and IrinotecanAlso: Temodar-Temozolomide, O6-Benzylguanine-O6-BG, Irinotecan-Camptosar-CPT 112 separate strata accrued independently: Stratum 1-pts receiving Dilantin, Tegretol or phenobarbital. Stratum 2-pts on anti-convulsants other than Dilantin, Tegretol/phenobarbital/pts not on any anti-convulsants. O6-BG administered intravenously 120mg/m2, over 1hr, prior to administration of Temozolomide on day 1 of 21day cycle. O6-BG administered intravenously 30mg/m2/day, over 48hrs, immediately after completion of CPT-11 infusion on day 1 of 21-day cycle. Temozolomide administered orally 355mg/m2 within 60 mins of end of 1hr O6-BG infusion. Treatment cycles may be repeated every 3wks following dose of Temozolomide from previous cycle. CPT-11 administered intravenously in fasting state over 90mins. CPT-11 infusion will begin 1hr after Temozolomide administration. Initial doses 60mg/m2 for stratum 1 \& 40mg/m2 for stratum2. Treatment cycles repeated every 3 wks following dose of CPT-11 from previous cycle. | Drug | 1, 2 |
Primary outcome
Incidence of toxicities
Time frame: 6 months
1 secondary outcome
Response rate & progression-free survival
Time frame: 6 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 19 Jun 2013.
- The Preston Robert Tisch Brain Tumor Center at DUKELink 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.
David A. Reardon, MD principal investigator
Duke Health
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 Temodar, O6-BG, and Irinotecan in people with Glioblastoma and Gliosarcoma, 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 16 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 19 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 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?
Incidence of toxicities (time frame: 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 19 Jun 2013.