GliosarcomaPhase 1NCT00612651
PH I Addition of Farnesyl Transferase Inhibitor to Temozolomide for Pts w Gr 3 & 4 Malignant Gliomas
A Phase 1 study testing Temodar and SCH 66336 in people with Gliosarcoma and Glioblastoma, run by Duke University at 1 site in United States.
Trial summary
Objectives: To determine maximum tolerated dose of farnesyl transferase inhibitor, SCH 66336, when administered w TEMODAR®. To characterize any toxicity associated w combo of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gliosarcoma, Glioblastoma, Anaplastic Astrocytoma
- What is being tested?
- Temodar and SCH 66336
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2005to Jun 2011
- 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 with MG histologically confirmed at diagnosis, who were treated previously with conventional external beam radiation \& with or without chemotherapy, \& have stable disease, recurrence or relapse at the time of enrollment.
- Age > or = to 18 years.
- Patients who have had previous surgical resection(s) are eligible.
- Interval of at least 3 weeks between prior surgical resection, 2 weeks between prior radiotherapy, or 4 weeks between prior chemotherapy, unless there is unequivocal evidence of tumor progression after surgery, radiotherapy, or chemotherapy.
- Karnofsky performance score > or = to 60%.
- Adequate hematologic, renal \& liver function as demonstrated by lab values performed within 14 days, inclusive, prior to administration of chemotherapy:
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- ANC > or = to 1500/mm3
- Platelet count > or = to 100,000/mm3
- Hemoglobin > or = to 10 gm/dL
- BUN and serum creatinine <1.5 times upper limit of lab normal
- Total serum bilirubin <1.5 times upper limit of lab normal
- SGOT <2.5 times upper limit of lab normal
- Patients must have recovered from any effects of major surgery.
- Patients must have life expectancy of greater than 12 weeks.
- Patients or legal guardian must give written, informed consent.
Who cannot join
- Patients requiring immediate radiation therapy.
- Patients who have not recovered from surgery.
- Patients who are not neurologically stable for 2 weeks prior to study entry.
- Patients who are poor medical risks because of non-malignant systemic disease as well as those with acute infection treated with intravenous antibiotics.
- Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
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- Known HIV positivity or AIDS-related illness.
- Pregnant or nursing women.
- Women of childbearing potential who are not using an effective method of contraception. Women of childbearing potential must have a negative serum pregnancy test 72 hours prior to administration of study drug and be practicing medically approved contraceptive precautions.
- Men who are not advised to use an effective method of contraception.
- Patients taking immuno-suppressive agents other than prescribed corticosteroids.
- Patients previously treated with farnesyl transferase inhibitors.
- Patients with significant QTc prolongation (>500 msec)as evaluated by an EKG.
- Patients having presented prior disease progression on TEMODAR.
- Patients having presented any grade 4 hematologic toxicity or grade 3 or 4 non-hematologic toxicity on TEMODAR in the past.
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: A Phase I Trial of the Addition of the Farnesyl Transferase Inhibitor, SCH 66336, to Temodar for Patients With Grade 3 and 4 Malignant Gliomas
Objectives:
To determine maximum tolerated dose of farnesyl transferase inhibitor, SCH 66336, when administered w TEMODAR®.
To characterize any toxicity associated w combo of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®.
To observe patients for clinical antitumor response when treated with combination of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®.
To assess pharmacokinetics of SCH 66336 for patients on \& not on enzyme inducing antiepileptic drugs.
Read the detailed description
2 separate strata accrued independently of each other: Stratum1-Patients receiving Dilantin, Tegretol / phenobarbital. Stratum2-Patients on anti-convulsants other than Dilantin, Tegretol / phenobarbital / Patients not on any anti-convulsants. Each stratum treated \& escalated independent of each other. Temozolomide administered orally at dose of 150mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles may be repeated every 4 weeks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice day, approximately every 12hrs. Initial doses will be 125mg BID for stratum 1 \& 75mg for stratum 2. Treatment cycles may be repeated every 4 weeks following dose of Temozolomide from previous cycle.
Subjects are patients with malignant glioma histologically confirmed at diagnosis, who were treated previously with conventional external beam radiation (XRT) \& with or without chemo, \& have stable disease, recurrence/relapse at time of enrollment. Approximately 48 subjects will be enrolled.
Temozolomide has been well tolerated by both adults \& children with 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 with Temozolomide. As is case with many anti-cancer drugs, Temozolomide may be carcinogenic. Rats given Temozolomide have developed breast cancer. Significance of this finding for humans is not presently known.
Significant adverse events observed for SCH66336 have included vomiting, diarrhea, anorexia, headaches, reversible renal toxicities, \& hematological toxicities. SCH 66336, although not genotoxic, inhibits rapidly proliferating cells \& at high doses inhibits spermatogenesis in male rats. It is not clear that inhibition of spermatogenesis is reversible,\& patients should be advised of possibility of irreversible sterility.
- Conditions
- Gliosarcoma, Glioblastoma, Anaplastic Astrocytoma
- Being tested
- Temodar and SCH 66336
- Keywords
- GBM, Malignant glioma, Brain tumor, Temodar, Temozolomide, SCH 66336, Farnesyl transferase inhibitor, Glioblastoma multiforme, Gliosarcoma, Anaplastic astrocytoma, Anaplastic oligodendroglioma, Anaplastic oligoastrocytoma
- Medical subject headings
- Gliosarcoma, Glioblastoma, Astrocytoma, Glioma, Brain Neoplasms, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Temodar and SCH 66336Drug
Also called Temodar-Temozolomide, Farnesyl transferase inhibitor-SCH 66336
2 separate strata accrued independently: Stratum 1-pts receiving CYP3A4-inducing anticonvulsants. Stratum 2-pts on non CYP3A4-inducing anticonvulsants or pts not on any anti-convulsants. Each strata treated \& escalated independent of each other. Temozolomide administered orally at dose of 150 mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200 mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles repeated every 4wks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice daily, approximately every 12hrs. Except as specifically noted, pts advised to take capsules wh morning \& evening meals, with approximately 240ml of non-carbonated water. Initial doses will be 125mg BID for stratum 1 \& 75mg BID for stratum2. Treatment cycles repeated every 4 wks following dose of Temozolomide from previous cycle.
| Study group | Role | What they receive |
|---|---|---|
| enzyme-inducing anti-epileptic drugs (EIAEDs) | Other | Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs)such as carbamazepine, phenobarbitol, phenytoin, phosphenytoin, oxcarbamazepine, primadone) Receives: Drug: Temodar and SCH 66336 |
| no enyzme-inducing anti-epileptic drugs | Other | Patients on non CYP3A4-inducing anti-convulsants or patients not on any anti-convulsants. Receives: Drug: Temodar and SCH 66336 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity
Measured: 6 months
Secondary outcomes (1)
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 startOct 2005
- Primary completionJan 2009
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GliosarcomaStudies 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
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough
- Responsible party
- Sponsor
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612651
- Sponsor's protocol ID
- Pro00005027
- Other IDs
- 7009/Pro00005027
- Status last verified
- Feb 2013
- First submitted
- 29 Jan 2008
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of the Addition of the Farnesyl Transferase Inhibitor, SCH 66336, to Temodar for Patients With Grade 3 and 4 Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00612651
- Acronym / sponsor ID
- Pro00005027
- Conditions
- Gliosarcoma, Glioblastoma, Anaplastic Astrocytoma
- Keywords
- GBM, Malignant glioma, Brain tumor, Temodar, Temozolomide, SCH 66336, Farnesyl transferase inhibitor, Glioblastoma multiforme
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Schering-Plough
- Study start
- Oct 2005
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jun 2011 (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 farnesyl transferase inhibitor, SCH 66336, when administered w TEMODAR®.
To characterize any toxicity associated w combo of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®.
To observe patients for clinical antitumor response when treated with combination of farnesyl transferase inhibitor, SCH 66336, \& TEMODAR®.
To assess pharmacokinetics of SCH 66336 for patients on \& not on enzyme inducing antiepileptic drugs.
Detailed description
2 separate strata accrued independently of each other: Stratum1-Patients receiving Dilantin, Tegretol / phenobarbital. Stratum2-Patients on anti-convulsants other than Dilantin, Tegretol / phenobarbital / Patients not on any anti-convulsants. Each stratum treated \& escalated independent of each other. Temozolomide administered orally at dose of 150mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles may be repeated every 4 weeks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice day, approximately every 12hrs. Initial doses will be 125mg BID for stratum 1 \& 75mg for stratum 2. Treatment cycles may be repeated every 4 weeks following dose of Temozolomide from previous cycle.
Subjects are patients with malignant glioma histologically confirmed at diagnosis, who were treated previously with conventional external beam radiation (XRT) \& with or without chemo, \& have stable disease, recurrence/relapse at time of enrollment. Approximately 48 subjects will be enrolled.
Temozolomide has been well tolerated by both adults \& children with 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 with Temozolomide. As is case with many anti-cancer drugs, Temozolomide may be carcinogenic. Rats given Temozolomide have developed breast cancer. Significance of this finding for humans is not presently known.
Significant adverse events observed for SCH66336 have included vomiting, diarrhea, anorexia, headaches, reversible renal toxicities, \& hematological toxicities. SCH 66336, although not genotoxic, inhibits rapidly proliferating cells \& at high doses inhibits spermatogenesis in male rats. It is not clear that inhibition of spermatogenesis is reversible,\& patients should be advised of possibility of irreversible sterility.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| enzyme-inducing anti-epileptic drugs (EIAEDs) | Other | Drug: Temodar and SCH 66336Patients receiving enzyme-inducing anti-epileptic drugs (EIAEDs)such as carbamazepine, phenobarbitol, phenytoin, phosphenytoin, oxcarbamazepine, primadone) |
| no enyzme-inducing anti-epileptic drugs | Other | Drug: Temodar and SCH 66336Patients on non CYP3A4-inducing anti-convulsants or patients 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 (15 listed)
- Pts with MG histologically confirmed at diagnosis, who were treated previously with conventional external beam radiation \& with or without chemotherapy, \& have stable disease, recurrence or relapse at the time of enrollment.
- Age > or = to 18 years.
- Patients who have had previous surgical resection(s) are eligible.
- Interval of at least 3 weeks between prior surgical resection, 2 weeks between prior radiotherapy, or 4 weeks between prior chemotherapy, unless there is unequivocal evidence of tumor progression after surgery, radiotherapy, or chemotherapy.
- Karnofsky performance score > or = to 60%.
Key exclusion criteria (15 listed)
- Patients requiring immediate radiation therapy.
- Patients who have not recovered from surgery.
- Patients who are not neurologically stable for 2 weeks prior to study entry.
- Patients who are poor medical risks because of non-malignant systemic disease as well as those with acute infection treated with intravenous antibiotics.
- Frequent vomiting or medical condition that could interfere with oral medication intake (e.g., partial bowel obstruction).
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 and SCH 66336Also: Temodar-Temozolomide, Farnesyl transferase inhibitor-SCH 663362 separate strata accrued independently: Stratum 1-pts receiving CYP3A4-inducing anticonvulsants. Stratum 2-pts on non CYP3A4-inducing anticonvulsants or pts not on any anti-convulsants. Each strata treated \& escalated independent of each other. Temozolomide administered orally at dose of 150 mg/m2 daily for 5 days, at bedtime, for 1st cycle \& escalated to 200 mg/m2 daily for 5 days, at bedtime during subsequent cycles if tolerated. Treatment cycles repeated every 4wks following doses of Temozolomide from previous cycle. SCH 66336 administered orally twice daily, approximately every 12hrs. Except as specifically noted, pts advised to take capsules wh morning \& evening meals, with approximately 240ml of non-carbonated water. Initial doses will be 125mg BID for stratum 1 \& 75mg BID for stratum2. Treatment cycles repeated every 4 wks following dose of Temozolomide from previous cycle. | Drug | enzyme-inducing anti-epileptic drugs (EIAEDs), no enyzme-inducing anti-epileptic drugs |
Primary outcome
Dose-limiting toxicity
Time frame: 6 months
1 secondary outcome
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 20 Feb 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.
Annick Desjardins, 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 and SCH 66336 in people with Gliosarcoma and Glioblastoma, 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 15 inclusion and 15 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 20 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 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?
Dose-limiting toxicity (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 20 Feb 2013.