Glioblastoma MultiformePhase 1/2NCT00050986

Phase I/II Evaluation of Temozolomide and ZARNESTRA (R115777) for Recurrent and Progressive Glioblastoma Multiforme

A Phase 1/2 study testing Temozolomide and R115777 in people with Glioblastoma Multiforme, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The goal of this clinical research study is to find the highest safe dose of the new drug ZARNESTRA (R115777) and temozolomide that can be given to patients with brain tumors (glioblastoma multiforme, GBM). The second goal is to learn if these drugs given in combination can shrink or slow the growth of brain tumors. Read more about this study

Who is it for?: Any age
Conditions the study is for: Glioblastoma Multiforme
What is being tested?: Temozolomide and R115777
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 55 participants
Where: 1 siteUnited States
Study dates: Dec 2002to Oct 2008
Phase: Phase 1/2
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 Any age
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Patients with histologically proven supratentorial glioblastoma multiforme (GBM).
Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan after radiation therapy. The scan done prior to study entry documenting progression will be reviewed by the primary investigator to document tumor volume changes to provide a gross assessment of growth rate.
Patients may have had: a) no prior chemotherapy, b) 1 prior adjuvant chemotherapy, c) 1 prior adjuvant chemotherapy followed by 1 regimen for recurrent disease, or d) 1 or 2 prior chemotherapy regimens for recurrent or progressive tumor.
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 CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline 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.
Pts with recent resection of recurrent or progressive tumor will be eligible if all of the following conditions apply: Pt has recovered from the effects of surgery; Residual disease after resection of recurrent tumor is not mandated for eligibility. To assess the extent of residual disease post-operatively, a CT/MRI should be done no later than 96 hours post-operatively or at least 4 weeks post-operatively, and within 14 days before registration. If steroid dose increased between the day of imaging and registration, a new baseline scan is required after stable steroids for 5 days.

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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.
Patients must have adequate bone marrow function (ANC>/= 1,500/mm(3) and platelet count of >/= 100,000/mm(3)), adequate liver function (SGPT and SGOT </= 2.5 times normal, bilirubin </= 2 mg%), and adequate renal function (BUN and creatinine <1.5 times institutional normal) prior to starting therapy.
ZARNESTRA may interfere with coumadin dosing and patients who are taking this combination will require more frequent monitoring of their PT, PTT and INR.
Patient has no risk factors for HIV or is serologically negative.

Who cannot join

Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants. Patients changing from these anticonvulsants to others that are allowed must be off the drugs listed above for at least 1 week.
Patients must not be taking cimetidine, erythromycin azole antifungals, paclitaxel, tacrolimus or cyclosporine.
Patients must not have uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia.
Because of the concerns of potentially harmful interactions of ZARNESTRA and other medications taken by patients who are HIV positive or have AIDS related diseases, patients who are HIV positive will not be eligible for entry into this study. Only patients with suspected HIV will be tested and if positive, will be ineligible.
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: a) active infection b) disease that will obscure toxicity or dangerously alter drug metabolism c) serious intercurrent medical illness. d) prior recurrence with either Temozolomide or a farnesyl transferase inhibitor.
Patients must not be pregnant and must practice adequate contraception

Trial locations and contacts

1 site in 1 country.

United States1 site

MD Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II Evaluation Temozolomide and Farnesyl Transferase Inhibitor ZARNESTRA (R115777) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme

Read the detailed description

Temozolomide works by killing cancer cells. R115777 is a new drug that may slow down the growth of cancer cells. Used in combination, the two drugs may control the growth of brain tumors.

Before treatment starts, patients will have a complete exam, including measurement of height and weight. Blood tests (less than 2 tablespoons of blood) will be performed. A MRI scan will be done. Women who are able have children must have a negative blood pregnancy test.

Temozolomide and R115777 will both be taken by mouth. Participants in this study will take temozolomide once a day for 7 days every other week (Days 1-7 and 15-21). This will be repeated every 28 days (1 course). Patients must not eat for 1 hour before and after taking the drug; drinking water is allowed. All treatment may be given on an outpatient basis.

During the alternate weeks (Days 8-14 and 22-28), participants will take R115777 tablets by mouth in the morning and evening with food. At the beginning of the study, groups of 3 participants each will take increasing doses of both R115777 and temozolomide until the highest safe dose of each drug, when given in combination, is found. Participants entering the study after the highest safe dose is found will receive that dosage.

If tumors do not grow and serious side effects do not occur, participants may keep on taking temozolomide and R115777 for up to 2 year. If your physician thinks it is advisable, treatment may continue with R115777 alone after that time. In this case, routine blood tests for counts, liver and kidney function (less than 2 tablespoons) will be repeated every 4 weeks and MRI scans, physical, and neurological exams will be done every 8 weeks. Participants may not receive any other treatment for cancer (including surgery) while taking part in this study.

Participants will come to the clinic to have a complete physical and neurological exam and blood tests (less than 2 tablespoons of blood) before each course. Blood tests will be repeated once a week for the first 2 courses of treatment and then on Days 14 and 28 of each later course. A MRI scan will be done before the odd-numbered (3, 5, 7, etc.) courses of treatment or at any time clinically indicated.

At the end of the study, participants will have another complete physical exam. Blood tests (less than 2 tablespoons of blood) will be performed. A MRI scan will be done.

This is an investigational study. Temozolomide is approved by the FDA for the treatment of some brain tumors and is commercially available. R115777 is approved for research use only in the treatment of brain tumors. The use of these two drugs together is experimental.

Conditions: Glioblastoma Multiforme
Being tested: Temozolomide, R115777
Keywords: Brain Neoplasms, CNS Diseases, Glioblastoma Multiforme, Temozolomide, Temodar, R115777, Zarnestra
Medical subject headings: Glioblastoma, Brain Neoplasms, Central Nervous System Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TemozolomideDrug
Also called Temodar
Starting Dose Level: 100 mg/m^2 taken by mouth once daily for 7 days, followed by 7 days rest and another 7-day dosing period and 7-day rest period.
R115777Drug
Also called Zarnestra
Starting Dose Level: 400 mg taken by mouth for 7 consecutive days every other week on alternating weeks (days 8-14 and 22-28) every 4 weeks.

Study groups in NCT00050986
Study group	Role	What they receive
Temozolomide and R115777	Experimental	Not described Receives: Drug: Temozolomide; Drug: R115777

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximal Tolerating Dose (MTD for Phase I)
Phase I Dose limiting toxicity evaluation at end of first cycle based on blood tests every two weeks and participants' subjective and objective symptoms.
Start Dose Level 100 mg/m² Temozolomide once daily + 400 mg ZARNESTRA twice daily; Dose Level 1 100 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 2 150 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 3 150 mg/m² Temozolomide once daily + 600 mg ZARNESTRA twice daily; Dose Level 4 150 mg/m² Temozolomide once daily + 800 mg ZARNESTRA twice daily
Measured: End of first cycle (4 weeks) evaluation

Secondary outcomes (1)

Progression-free Survival (Phase II)
Efficacy measured by 6 month progression-free survival assessment.
Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2002Oct 2008

First posted3 Jan 2003 (estimated)
Study startDec 2002
Primary completionOct 2008
Study completionOct 2008

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 Glioblastoma MultiformeStudies 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 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 55 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00050986
Sponsor's protocol ID: ID02-126
Status last verified: Sep 2020
First submitted: 31 Dec 2002
Last updated: 22 Sep 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

All Glioblastoma Multiforme trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Evaluation Temozolomide and Farnesyl Transferase Inhibitor ZARNESTRA (R115777) for the Treatment of Recurrent and Progressive Glioblastoma Multiforme
ClinicalTrials.gov ID: NCT00050986
Acronym / sponsor ID: ID02-126
Conditions: Glioblastoma Multiforme
Keywords: Brain Neoplasms, CNS Diseases, Glioblastoma Multiforme, Temozolomide, Temodar, R115777, Zarnestra
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 55 participants (actual)
Lead sponsor: M.D. Anderson Cancer CenterUniversity, hospital or other
Collaborators: Johnson & Johnson
Study start: Dec 2002
Primary completion: Oct 2008 (actual)
Study completion: Oct 2008 (actual)
First posted: 3 Jan 2003 (estimated)
Results: Posted 16 Sep 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Temozolomide works by killing cancer cells. R115777 is a new drug that may slow down the growth of cancer cells. Used in combination, the two drugs may control the growth of brain tumors.

At the end of the study, participants will have another complete physical exam. Blood tests (less than 2 tablespoons of blood) will be performed. A MRI scan will be done.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Temozolomide and R115777	Experimental	Drug: Temozolomide, Drug: R115777

Who may qualify

Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (11 listed)

Patients with histologically proven supratentorial glioblastoma multiforme (GBM).
Patients must have shown unequivocal evidence for tumor recurrence or progression by MRI scan after radiation therapy. The scan done prior to study entry documenting progression will be reviewed by the primary investigator to document tumor volume changes to provide a gross assessment of growth rate.
Patients may have had: a) no prior chemotherapy, b) 1 prior adjuvant chemotherapy, c) 1 prior adjuvant chemotherapy followed by 1 regimen for recurrent disease, or d) 1 or 2 prior chemotherapy regimens for recurrent or progressive tumor.
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 CT scan. A scan should be performed within 14 days prior to registration and on a steroid dose that has been stable for at least 5 days. If the steroid dose is increased between the date of imaging and registration a new baseline 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 (7 listed)

Patients must not be taking primidone, carbamazepine, phenobarbital or phenytoin anticonvulsants. Patients changing from these anticonvulsants to others that are allowed must be off the drugs listed above for at least 1 week.
Patients must not be taking cimetidine, erythromycin azole antifungals, paclitaxel, tacrolimus or cyclosporine.
Patients must not have uncontrolled high blood pressure, unstable angina, symptomatic congestive heart failure, myocardial infarction within the previous six months, or serious uncontrolled cardiac arrhythmia.
Because of the concerns of potentially harmful interactions of ZARNESTRA and other medications taken by patients who are HIV positive or have AIDS related diseases, patients who are HIV positive will not be eligible for entry into this study. Only patients with suspected HIV will be tested and if positive, will be ineligible.
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.

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
TemozolomideAlso: TemodarStarting Dose Level: 100 mg/m^2 taken by mouth once daily for 7 days, followed by 7 days rest and another 7-day dosing period and 7-day rest period.	Drug	Temozolomide and R115777
R115777Also: ZarnestraStarting Dose Level: 400 mg taken by mouth for 7 consecutive days every other week on alternating weeks (days 8-14 and 22-28) every 4 weeks.	Drug	Temozolomide and R115777

Primary outcome

Maximal Tolerating Dose (MTD for Phase I)
Time frame: End of first cycle (4 weeks) evaluation
Phase I Dose limiting toxicity evaluation at end of first cycle based on blood tests every two weeks and participants' subjective and objective symptoms. Start Dose Level 100 mg/m² Temozolomide once daily + 400 mg ZARNESTRA twice daily; Dose Level 1 100 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 2 150 mg/m² Temozolomide once daily + 500 mg ZARNESTRA twice daily; Dose Level 3 150 mg/m² Temozolomide once daily + 600 mg ZARNESTRA twice daily; Dose Level 4 150 mg/m² Temozolomide once daily + 800 mg ZARNESTRA twice daily

1 secondary outcome

Progression-free Survival (Phase II)
Time frame: 6 months

Results and safety

Results posted to the registry on 16 Sep 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Temozolomide and R115777	55	53

Primary outcome: Maximal Tolerating Dose (MTD for Phase I)

Time frame: End of first cycle (4 weeks) evaluation. Number. Unit: participants

Measure	Temozolomide and R115777 n = 15
Dose Level 1	3
Dose Level 2	3
Dose Level 3	6
Dose Level 4	3

Population analysed: As treated.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: 2 years, 11 months. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Temozolomide and R115777	24 of 53 (45.3%)	47 of 53 (88.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
UT MD Anderson Cancer Center websiteLink provided by the sponsor.

Related trials for Glioblastoma Multiforme

Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma

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.

Mark R. Gilbert principal investigator

MDAnderson 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 1/2 study testing Temozolomide and R115777 in people with Glioblastoma Multiforme, 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 11 inclusion and 7 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 22 Sep 2020. 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 combined 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.

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 16 Sep 2010). 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?

Maximal Tolerating Dose (MTD for Phase I) (time frame: End of first cycle (4 weeks) evaluation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00050986.

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 22 Sep 2020.