Adult Giant Cell GlioblastomaPhase 1NCT02227901
Tipifarnib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
A Phase 1 study testing Tipifarnib, External Beam Radiation Therapy and Temozolomide in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of tipifarnib when given together with radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme. Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- Tipifarnib, External Beam Radiation Therapy and Temozolomide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2002to Apr 2014
- 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 will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS)
- Diagnosis will have been established by biopsy or resection within 4 weeks prior to registration
- Patients must not have received previous radiotherapy to the brain
- Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent complications
- Cranial magnetic resonance imaging (MRI) or contrast computed tomography (CT) must have been performed within 21days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed with 96 hours of resection is preferred but not required; patients without measurable or assessable disease are eligible
- Patients must have a plan to begin partial brain radiotherapy within 5-9 days after beginning R115777, and within 35 days (5 weeks) of the surgical procedure that established the diagnosis; radiotherapy must be given at the Radiation Oncology Department of the registering Adult Brain Tumor Consortium (ABTC) institution; radiotherapy must be given by external beam to a partial brain field in daily fractions of 2.0 Gray (Gy), to a planned total dose to the tumor of 60.0 Gy; stereotactic radiosurgery and brachytherapy will not be allowed
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- Patients must be willing to forego other drug therapy against the tumor while being treated with R115777 and temozolomide
- All patients must sign an informed consent indicating that they are aware of the investigational nature of this study; patients must sign an authorization for the release of their protected health information; patients must be registered with the Adult Brain Tumor Consortium Central Office (ABTC CO) prior to treatment with study drug
- A life expectancy > 8 weeks
- Patients must have a Karnofsky performance status of >= 60
- White blood cells (WBC) >= 3,000/ul
- Absolute neutrophil count (ANC) >= 1,500/mm^3
- Platelet count of >= 100,000/mm^3
- Hemoglobin >= 10 gm/dl
- Bone marrow function tests must be performed within 14 days prior to registration
- Eligibility level for hemoglobin may be reached by transfusion
- Serum glutamic oxaloacetic transaminase (SGOT) < 2 times upper limit of normal (ULN) and the test must be performed within 14 days prior to registration; if above the institutional upper limit of normal but < 2 times institutional upper limit of normal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
- Bilirubin < 2 times ULN and the test must be performed within 14 days prior to registration; if above the institutional upper limit of normal but < 2 times institutional upper limit of normal, the decision to initiate temozolomide treatment should carefully consider the benefits and risks for the individual patient
- Creatinine < 1.5 mg/dL before starting therapy and the test must be performed within 14 days prior to registration
- Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy; patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism
- Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible
- No exclusion to this study will be based on race; minorities will actively be recruited to participate
- Patients must not have active infection
- Women must not be pregnant or breast-feeding, and women with reproductive potential must practice adequate contraception
- Patients must not be on chronic Coumadin therapy for prior medical problems (e.g. cardiac valve prophylaxis); this is due to a presumed interaction with Coumadin and ZARNESTRA leading to a significant increase in international normalized ratio (INR); patients who develop or have recently developed a deep venous thrombosis or pulmonary embolism who are on or will take Coumadin will be allowed to participate; however, the investigator should be prepared to monitor patients INR closely
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
About this study
Official title: Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
This phase I trial studies the side effects and best dose of tipifarnib when given together with radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme. Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. 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 tipifarnib together with radiation therapy and temozolomide may be a better way to treat glioblastoma multiforme.
Read the detailed description
PRIMARY OBJECTIVES:
- Establish maximum tolerated dose (MTD) for tipifarnib (R115777) in combination with temozolomide with radiation in patients not on enzyme-inducing anti-epileptic drugs (EIAEDs).
II. To define the safety of R115777 in combination with temozolomide with radiation in this patient population.
III. To assess for evidence of antitumor activity in this patient population.
OUTLINE: This is a dose-escalation study of tipifarnib.
TIPIFARNIB: Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CONCURRENT CHEMOTHERAPY DURING RADIATION THERAPY: Within 5-9 days after starting tipifarnib, patients undergo external beam radiation therapy (EBRT) daily and receive temozolomide PO daily for 6 weeks.
POST-RADIATION CHEMOTHERAPY: Beginning at week 10 post-radiation therapy, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for 1 year or 12 complete courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 months.
- Being tested
- Tipifarnib, External Beam Radiation Therapy, Temozolomide, Laboratory Biomarker Analysis
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TipifarnibDrug
Also called R115777, Zarnestra
Given PO
External Beam Radiation TherapyRadiation
Also called Definitive Radiation Therapy, EBRT, External Beam RT
Undergo EBRT
TemozolomideDrug
Also called TMZ
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tipifarnib, EBRT, temozolomide) | Experimental | TIPIFARNIB: Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CONCURRENT CHEMOTHERAPY DURING RADIATION THERAPY: Within 5-9 days after starting tipifarnib, patients undergo EBRT daily and receive temozolomide PO daily for 6 weeks.
POST-RADIATION CHEMOTHERAPY: Beginning at week 10 post-radiation therapy, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for 1 year or 12 complete courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: Tipifarnib; Radiation: External Beam Radiation Therapy; Drug: Temozolomide; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity (DLT) of tipifarnib, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0
Safety variables will be summarized by descriptive statistics.
Measured: At week 10
MTD of tipifarnib, defined as the dose level at which 0 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT, graded according to the NCI CTCAE v4.0
Safety variables will be summarized by descriptive statistics.
Measured: Up to week 10
Secondary outcomes (2)
Incidence of adverse events of tipifarnib in combination with EBRT and temozolomide, graded according to the NCI CTCAE v4.0
Safety variables will be summarized by descriptive statistics. Adverse events that occur will be reported for each dose level and described in terms of incidence and severity. Parameters will be described based on the CTCAE severity grading. Distribution by CTCAE severity grade (when applicable) and clinical relevance will be given.
Measured: Up to 5 years
Anti-tumor activity of tipifarnib
A descriptive analysis of evidence of antitumor activity will be provided based on clinical, radiographic, and biologic assessments of efficacy.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2014 (estimated)
- Study startSep 2002
- Primary completionJun 2007
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Timothy Cloughesy, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02227901
- Sponsor's protocol ID
- NCI-2014-01809
- Other IDs
- NCI-2014-01809, NCI-03-C-0189, NABTC-0202, NABTC02-02, NABTC-02-02, U01CA062399
- Status last verified
- Sep 2014
- First submitted
- 26 Aug 2014
- Last updated
- 23 Dec 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of R115777 With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT02227901
- Acronym / sponsor ID
- NCI-2014-01809
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2002
- Primary completion
- Jun 2007 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 28 Aug 2014 (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 tipifarnib when given together with radiation therapy and temozolomide in treating patients with newly diagnosed glioblastoma multiforme. Tipifarnib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x rays to kill tumor cells. 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 tipifarnib together with radiation therapy and temozolomide may be a better way to treat glioblastoma multiforme.
Detailed description
PRIMARY OBJECTIVES:
- Establish maximum tolerated dose (MTD) for tipifarnib (R115777) in combination with temozolomide with radiation in patients not on enzyme-inducing anti-epileptic drugs (EIAEDs).
II. To define the safety of R115777 in combination with temozolomide with radiation in this patient population.
III. To assess for evidence of antitumor activity in this patient population.
OUTLINE: This is a dose-escalation study of tipifarnib.
TIPIFARNIB: Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
CONCURRENT CHEMOTHERAPY DURING RADIATION THERAPY: Within 5-9 days after starting tipifarnib, patients undergo external beam radiation therapy (EBRT) daily and receive temozolomide PO daily for 6 weeks.
POST-RADIATION CHEMOTHERAPY: Beginning at week 10 post-radiation therapy, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for 1 year or 12 complete courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tipifarnib, EBRT, temozolomide) | Experimental | Drug: Tipifarnib, Radiation: External Beam Radiation Therapy, Drug: Temozolomide, Other: Laboratory Biomarker AnalysisTIPIFARNIB: Patients receive tipifarnib PO BID on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. CONCURRENT CHEMOTHERAPY DURING RADIATION THERAPY: Within 5-9 days after starting tipifarnib, patients undergo EBRT daily and receive temozolomide PO daily for 6 weeks. POST-RADIATION CHEMOTHERAPY: Beginning at week 10 post-radiation therapy, patients receive temozolomide PO on days 1-5. Treatment repeats every 28 days for 1 year or 12 complete 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 (25 listed)
- Patients will have histologically proven intracranial glioblastoma multiforme (GBM) or gliosarcoma (GS)
- Diagnosis will have been established by biopsy or resection within 4 weeks prior to registration
- Patients must not have received previous radiotherapy to the brain
- Patients must not have received cytotoxic drug therapy, non-cytotoxic drug therapy, or experimental drug therapy directed against the brain tumor; patients who received Gliadel wafers will be excluded; patients may have received or be receiving corticosteroids, non-EIAEDs, analgesics, and other drugs to treat symptoms or prevent complications
- Cranial magnetic resonance imaging (MRI) or contrast computed tomography (CT) must have been performed within 21days of study entry; the use of MRI rather than CT is preferred; the same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement; if the surgical procedure was a resection, cranial MRI or contrast CT performed with 96 hours of resection is preferred but not required; patients without measurable or assessable disease are eligible
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| TipifarnibAlso: R115777, ZarnestraGiven PO | Drug | Treatment (tipifarnib, EBRT, temozolomide) |
| External Beam Radiation TherapyAlso: Definitive Radiation Therapy, EBRT, External Beam RTUndergo EBRT | Radiation | Treatment (tipifarnib, EBRT, temozolomide) |
| TemozolomideAlso: TMZGiven PO | Drug | Treatment (tipifarnib, EBRT, temozolomide) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (tipifarnib, EBRT, temozolomide) |
Primary outcome
Dose limiting toxicity (DLT) of tipifarnib, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0
Time frame: At week 10
Safety variables will be summarized by descriptive statistics.
MTD of tipifarnib, defined as the dose level at which 0 or 1/6 patients experience DLT with the next higher dose having at least 2/3 or 2/6 patients encountering DLT, graded according to the NCI CTCAE v4.0
Time frame: Up to week 10
Safety variables will be summarized by descriptive statistics.
2 secondary outcomes
Incidence of adverse events of tipifarnib in combination with EBRT and temozolomide, graded according to the NCI CTCAE v4.0
Time frame: Up to 5 years
Anti-tumor activity of tipifarnib
Time frame: Up to 5 years
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 23 Dec 2014.
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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 Cloughesy principal investigator
National Cancer Institute (NCI)
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 Tipifarnib, External Beam Radiation Therapy and Temozolomide in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) 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 25 inclusion and 0 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 23 Dec 2014. 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 (DLT) of tipifarnib, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 (time frame: At week 10). 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 23 Dec 2014; AzTrials last refreshed its copy on 7 Nov 2026.