Malignant Supratentorial NeoplasmPhase 1NCT00102648
Lonafarnib and Temozolomide in Treating Patients with Glioblastoma Multiforme That is Recurrent or Did Not Respond to Previous Treatment with Temozolomide
A Phase 1 study testing Lonafarnib and Temozolomide in people with Malignant Supratentorial Neoplasm and Recurrent Glioblastoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of lonafarnib when given together with temozolomide and to see how well they work in treating patients with glioblastoma multiforme that is has come back or did not respond to previous treatment with temozolomide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Supratentorial Neoplasm, Recurrent Glioblastoma, Recurrent Gliosarcoma
- What is being tested?
- Lonafarnib and Temozolomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Dec 2004to 1 Dec 2025
- 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
- Patients with histologically proven supratentorial glioblastoma multiforme (GBM) or gliosarcoma
- Patients must have shown unequivocal evidence for tumor recurrence or progression by magnetic resonance imaging (MRI) scan after radiation therapy; the scan done prior to study entry documenting progression will be reviewed by the treating physician to document tumor volume changes to provide a gross assessment of growth rate
- Patients may have had as many as 2 prior chemotherapy regimens for recurrent or progressive tumor; patients must have had prior treatment with Temodar but may not have had prior treatment with farnesyl transferase inhibitors (Sarasar or Zarnestra); patients in phase 1b expansion are required to have received a minimum of two cycles of adjuvant temozolomide (TMZ)
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital
- Patients must have shown unequivocal evidence for tumor progression by MRI or computed tomography (CT) scan; a scan should be performed within 14 days prior to registration and on a steroid dose that has been stable or decreasing for at least 5 days; if the steroid dose is increased between the date of imaging and registration a new baseline magnetic resonance (MR)/CT is required; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement
- Patients (pts) having had recent resection of recurrent or progressive tumor are eligible as long as:
Show all 17Show fewer
- Patients must be status post surgical resection at least 2 weeks prior to study enrollment, have recovered from surgery, have adequate early wound healing and a Karnofsky performance status of > or = 60
- Residual disease following resection of recurrent tumor is not mandated for eligibility into the study; a CT/MRI should be done within 96 hours (hrs) post-op or at least 4 weeks (wks) post-op (within 14 days of registration); if the steroid dose is increased between the scan date and registration, a new baseline MRI/CT is required on a stable steroid dose for 5 days
- Patients must have a Karnofsky performance status of >= 60
- Patients must have recovered from the toxic effects of prior therapy: 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 6 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count); any questions related to the definition of non-cytotoxic agents should be directed to the study chair
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count of >= 100,000/mm^3
- Serum glutamic pyruvate transaminase (SGPT) < 2.5 times normal
- Alkaline phosphatase < 2.5 times normal
- Bilirubin < 1.5 mg
- Blood urea nitrogen (BUN) < 1.5 times institutional normal
- Creatinine < 1.5 times institutional normal
Who cannot join
- Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants; patients changing from these anticonvulsants to other allowable drugs that are not enzyme inducing antiepileptic drugs (EIAEDs) must be off the drugs listed above for at least 72 hours prior the initiation of treatment
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), are ineligible unless in complete remission and off of all therapy for that disease for a minimum of 3 years
- Patients must not have:
- Uncontrolled active infection
- Disease that will obscure toxicity or dangerously alter drug metabolism
- Serious intercurrent medical illness
- Prior recurrence with a farnesyl transferase inhibitor
- Oral contraceptives and other hormonal methods (Depo-Provera) of birth control
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/Ib Study of Sarasar and Temodar in Patients with Recurrent or Temodar-Refractory Glioblastoma Multiforme
This phase I trial studies the side effects and best dose of lonafarnib when given together with temozolomide and to see how well they work in treating patients with glioblastoma multiforme that is has come back or did not respond to previous treatment with temozolomide. Lonafarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lonafarnib together with temozolomide may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose Sarasar (SCH66336, lonafarnib) when combined with Temodar (temozolomide) in an alternating week schedule.
II. To describe the toxicities of the Sarasar and Temodar combination treatment using this dosing schedule.
III. To evaluate response as measured by 6-month progression-free survival and objective tumor response.
OUTLINE: This is a dose-escalation study of lonafarnib.
Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 and 15-21 and lonafarnib PO twice daily (BID) on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
- Being tested
- Lonafarnib, Temozolomide
- Medical subject headings
- Supratentorial Neoplasms, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LonafarnibDrug
Also called 4-[2-[4-[(11R)-3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxamide, Sarasar, SCH 66336, SCH-66336
Given PO
TemozolomideDrug
Also called CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (temozolomide and lonafarnib) | Experimental | Patients receive temozolomide PO QD on days 1-7 and 15-21 and lonafarnib PO BID on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Lonafarnib; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of lonafarnib when given with temozolomide, defined as the dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT)
Measured: 28 days
Tolerability of regimen in patients with disease progression or recurrence during or after recent completion of treatment with temozolomide
Measured: Up to 11 years
Secondary outcomes (4)
Progression free survival (PFS)
In the historical dataset, the proportion of patients remaining alive and free from progression at 6 months was 15% (95% confidence interval for ranged from 10% to 19%). We will set p0 to 15% and we will set p1 to 30% (looking for a doubling of the 6-month PFS rate). Based on these design parameters, a two-stage design would require that at least 4 of the initial 19 patients are without progression at 6 months.
Measured: 6 months
Objective response
Measured: Up to 11 years
Overall survival
Measured: Up to 11 years
Treatment-related toxicities
Treatment-related toxicity data will be collected and described.
Measured: Up to 11 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2005 (estimated)
- Study start21 Dec 2004
- Primary completion1 Mar 2025 (estimated)
- Study completion1 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Supratentorial NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- Not applicable
- Intervention model
- Single group
- Enrolment
- 34 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Vinay Puduvalli, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00102648
- Sponsor's protocol ID
- 2004-0424
- Other IDs
- NCI-2012-01311, NCI-2010-00417, 2004-0424
- Status last verified
- Oct 2024
- First submitted
- 31 Jan 2005
- Last updated
- 17 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/Ib Study of Sarasar and Temodar in Patients with Recurrent or Temodar-Refractory Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00102648
- Acronym / sponsor ID
- 2004-0424
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (estimated)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 21 Dec 2004 (actual)
- Primary completion
- 1 Mar 2025 (estimated)
- Study completion
- 1 Dec 2025 (estimated)
- First posted
- 1 Feb 2005 (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.
This phase I trial studies the side effects and best dose of lonafarnib when given together with temozolomide and to see how well they work in treating patients with glioblastoma multiforme that is has come back or did not respond to previous treatment with temozolomide. Lonafarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lonafarnib together with temozolomide may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose Sarasar (SCH66336, lonafarnib) when combined with Temodar (temozolomide) in an alternating week schedule.
II. To describe the toxicities of the Sarasar and Temodar combination treatment using this dosing schedule.
III. To evaluate response as measured by 6-month progression-free survival and objective tumor response.
OUTLINE: This is a dose-escalation study of lonafarnib.
Patients receive temozolomide orally (PO) once daily (QD) on days 1-7 and 15-21 and lonafarnib PO twice daily (BID) on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (temozolomide and lonafarnib) | Experimental | Drug: Lonafarnib, Drug: TemozolomidePatients receive temozolomide PO QD on days 1-7 and 15-21 and lonafarnib PO BID on days 8-14 and 22-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients with histologically proven supratentorial glioblastoma multiforme (GBM) or gliosarcoma
- Patients must have shown unequivocal evidence for tumor recurrence or progression by magnetic resonance imaging (MRI) scan after radiation therapy; the scan done prior to study entry documenting progression will be reviewed by the treating physician to document tumor volume changes to provide a gross assessment of growth rate
- Patients may have had as many as 2 prior chemotherapy regimens for recurrent or progressive tumor; patients must have had prior treatment with Temodar but may not have had prior treatment with farnesyl transferase inhibitors (Sarasar or Zarnestra); patients in phase 1b expansion are required to have received a minimum of two cycles of adjuvant temozolomide (TMZ)
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of this hospital
- Patients must have shown unequivocal evidence for tumor progression by MRI or computed tomography (CT) scan; a scan should be performed within 14 days prior to registration and on a steroid dose that has been stable or decreasing for at least 5 days; if the steroid dose is increased between the date of imaging and registration a new baseline magnetic resonance (MR)/CT is required; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement
Key exclusion criteria (8 listed)
- Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants; patients changing from these anticonvulsants to other allowable drugs that are not enzyme inducing antiepileptic drugs (EIAEDs) must be off the drugs listed above for at least 72 hours prior the initiation of treatment
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), are ineligible unless in complete remission and off of all therapy for that disease for a minimum of 3 years
- Patients must not have:
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 |
|---|---|---|
| LonafarnibAlso: 4-[2-[4-[(11R)-3,10-Dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl]-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxamide, Sarasar, SCH 66336, SCH-66336Given PO | Drug | Treatment (temozolomide and lonafarnib) |
| TemozolomideAlso: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831Given PO | Drug | Treatment (temozolomide and lonafarnib) |
Primary outcome
Maximum tolerated dose (MTD) of lonafarnib when given with temozolomide, defined as the dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT)
Time frame: 28 days
Tolerability of regimen in patients with disease progression or recurrence during or after recent completion of treatment with temozolomide
Time frame: Up to 11 years
4 secondary outcomes
Progression free survival (PFS)
Time frame: 6 months
Objective response
Time frame: Up to 11 years
Overall survival
Time frame: Up to 11 years
Treatment-related toxicities
Time frame: Up to 11 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
- MD Anderson Cancer 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.
Vinay Puduvalli principal investigator
M.D. Anderson Cancer Center
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 Lonafarnib and Temozolomide in people with Malignant Supratentorial Neoplasm and Recurrent Glioblastoma, run by M.D. Anderson Cancer Center 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 17 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 17 Oct 2024. 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?
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?
Maximum tolerated dose (MTD) of lonafarnib when given with temozolomide, defined as the dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) (time frame: 28 days). The study lists 2 primary outcomes in all. 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 17 Oct 2024.