Untreated Childhood Brain Stem GliomaPhase 1/2NCT00079339
Tipifarnib and Radiation Therapy in Treating Young Patients With Brainstem Glioma
A Phase 1/2 study testing radiation therapy and tipifarnib in people with Untreated Childhood Brain Stem Glioma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Tipifarnib may make tumor cells more sensitive to radiation therapy. Combining tipifarnib with radiation therapy may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 21 years
- Conditions the study is for
- Untreated Childhood Brain Stem Glioma
- What is being tested?
- radiation therapy and tipifarnib
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Nov 2009
- 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 3 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Newly diagnosed non-disseminated intrinsic diffuse brainstem glioma
- Karnofsky performance scale (KPS) (for > 16 yrs of age) or Lansky performance score (LPS) (for =< 16 years of age) => 50 assessed within two weeks prior to registration
- Prior/concurrent therapy:
- Chemo: No prior therapy allowed
- Radiation therapy (XRT): No prior therapy allowed
- Bone Marrow Transplant: None prior
Show all 17Show fewer
- Anti-convulsants: Patients receiving EIACDs will not be eligible; however, patients may switch from EIACDs to non-EIACDs and must then be on non-EIACDs for a minimum of 7 days prior to registration
- Growth factors: Off all colony forming growth factor(s) > 2 weeks prior to registration (G-CSF, GM-CSF, erythropoietin)
- Absolute neutrophil count >= 1,000/mm^3
- Platelets >= 100,000/mm^3 (transfusion independent)
- Hemoglobin >= 8 gm/dL (transfusion independent)
- Serum creatinine that is less than the upper limit of institutional normal for age or GFR > 70 ml/min/1.73m2
- Bilirubin =< 1.5 time upper limit of normal for age
- SGPT (ALT) and SGOT (AST) < 2.5 times institutional upper limit of normal
- Female patients of childbearing potential must have negative serum or urine pregnancy test; patient must not be pregnant or breast-feeding
- Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study
- Signed informed consent according to institutional guidelines must be obtained
Who cannot join
- 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 disseminated intrinsic diffuse brainstem glioma
- Patients taking enzyme-inducing anticonvulsant drugs
- Patients with known allergy to topical or systemic imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole)
- Patients receiving any other anticancer or experimental drug therapy
- Patients with uncontrolled infection
Trial locations and contacts
1 site in 1 country.
United States1 site
Pediatric Brain Tumor Consortium
Memphis, Tennessee, 38105
About this study
Official title: Phase I/II Trial of R115777 and XRT in Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas
Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Tipifarnib may make tumor cells more sensitive to radiation therapy. Combining tipifarnib with radiation therapy may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of tipifarnib to see how well it works when given together with radiation therapy in treating young patients with newly diagnosed brain stem glioma. (Phase I closed to accrual as of 1/19/06)
Read the detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) of R115777 administered concurrently with radiation therapy to pediatric patients with non-disseminated, diffuse, intrinsic brainstem gliomas who are not receiving enzyme-inducing anti-convulsant drugs (EIACD).
II. To assess the efficacy of R115777 treatment in combination with radiation therapy for patients with non-disseminated, diffuse, intrinsic pontine gliomas as measured by progression-free survival and survival distributions.
SECONDARY OBJECTIVES:
- To characterize toxicities associated with R115777 treatment in combination with and post radiation therapy.
II. To characterize radiographic changes in brainstem gliomas treated with radiation and R115777 using MRI, perfusion and diffusion imaging and PET scans.
OUTLINE: This is a phase I (closed to accrual as of 1/19/06), multicenter, dose-escalation study of tipifarnib followed by a phase II safety and efficacy study.
PHASE I: Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses (total of 26 courses) in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib during radiotherapy until the maximum tolerated dose is determined. The MTD is defined as the dose level preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/19/06). Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity.
FOLLOW-UP:
Phase I: Participants contributing only to the phase I part are followed for 90 days after completion of therapy. Adverse events that have not resolved within 90 days after stopping treatment will be followed until resolution.
Phase II: Participants in the phase I part treated at the MTD or participants in the phase II part are followed until the earliest of death or three years after starting treatment.
PROJECTED ACCRUAL: A total of 3-55 patients (3-18 patients for phase I [closed to accrual as of 1/19/06] and a total of 40 patients for phase II [including 6 patients treated in the dose-finding portion of phase I (closed to accrual as of 1/19/06)]) will be accrued for this study within 2.3 years.
- Conditions
- Untreated Childhood Brain Stem Glioma
- Being tested
- radiation therapy, tipifarnib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
radiation therapyRadiation
Also called irradiation, radiotherapy, therapy, radiation
Undergo radiotherapy
tipifarnibDrug
Also called R115777, Zarnestra
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatment (radiation therapy and tipifarnib) | Experimental | PHASE I: Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses (total of 26 courses) in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/19/06). Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity. Receives: Radiation: radiation therapy; Drug: tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy
The dose limiting toxicity (DLT) analysis population consists of phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD.
Measured: Day 1 of tipifarnib therapy to week 8
Progression-free Survival (PFS)
PFS was defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.
Measured: Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks.
Secondary outcomes (5)
Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation
This study attempted to investigate in an exploratory manner the effect of treatment on changes in neuroimaging meaurements. Neuroimaging changes may have some association with outcome (response, survival, etc.). Perfusion values are obtained from magnetic resonance perfusion imaging and were measured at baseline, every 8 weeks for the first 48 weeks, and then every 12 weeks until treatment is discontinued.
Measured: Baseline and two weeks post completion of radiation
Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation.
This study attempted to investigate in an exploratory manner the effect of treatment on changes in neuroimaging meaurements. Neuroimaging changes may have some association with outcome (response, survival, etc.). Diffusion values are obtained from magnetic resonance diffusion imaging and were measured at baseline, every 8 weeks for the first 48 weeks, and then every 12 weeks until treatment is discontinued.
Measured: Baseline and two weeks post completion of radiation
Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation
This study attempted to investigate in an exploratory manner the effect of treatment on changes in various neuroimaging variables. Neuroimaging changes may have some association with outcome (response, survival, etc.). Volume FLAIR is one parameter obtained from standard magnetic resonance imaging (MRI) studies of the brain. Volume FLAIR was obtained at baseline and within two weeks after completion of radiation.
Measured: Baseline and two weeks post completion of radiation
Mean Tumor to Gray Matter Ratio Measured at Baseline
This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal gray matter to provide ratios of tumor/gray matter. Each patient has a mean tumor to gray matter ratio value and the median of these values across patients is reported.
Measured: Baseline
Mean Tumor to White Matter Ratio Measured at Baseline
This study attempts to characterize neuroimaging parameters from positron emission tomography. For each patient, the axial image through the tumor containing the maximum activity per pixel corresponding to the highest FluoroDeoxyGlucose (FDG) uptake was identified and a region of interest (ROI) was drawn based on the FDG definition of the tumor. The mean pixel values within the tumor ROI were normalized by those for normal white matter to provide ratios of tumor/white matter. Each patient has a mean tumor to white matter ratio value and the median of these values across patients is reported.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2004 (estimated)
- Study startJan 2004
- Primary completionNov 2009
- Study completionNov 2009
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 Untreated Childhood Brain Stem GliomaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Daphne Haas-Kogan, Principal investigator, Pediatric Brain Tumor Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00079339
- Sponsor's protocol ID
- NCI-2012-03021
- Other IDs
- NCI-2012-03021, PBTC-014, PBTC-014, U01CA081457
- Status last verified
- Dec 2012
- First submitted
- 8 Mar 2004
- Last updated
- 15 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of R115777 and XRT in Pediatric Patients With Newly Diagnosed Non-Disseminated Intrinsic Diffuse Brainstem Gliomas
- ClinicalTrials.gov ID
- NCT00079339
- Acronym / sponsor ID
- NCI-2012-03021
- Conditions
- Untreated Childhood Brain Stem Glioma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2004
- Primary completion
- Nov 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 10 Mar 2004 (estimated)
- Results
- Posted 24 Sep 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Radiation therapy uses high-energy x-rays to damage tumor cells. Tipifarnib may make tumor cells more sensitive to radiation therapy. Combining tipifarnib with radiation therapy may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of tipifarnib to see how well it works when given together with radiation therapy in treating young patients with newly diagnosed brain stem glioma. (Phase I closed to accrual as of 1/19/06)
Detailed description
PRIMARY OBJECTIVES:
- To estimate the maximum tolerated dose (MTD) of R115777 administered concurrently with radiation therapy to pediatric patients with non-disseminated, diffuse, intrinsic brainstem gliomas who are not receiving enzyme-inducing anti-convulsant drugs (EIACD).
II. To assess the efficacy of R115777 treatment in combination with radiation therapy for patients with non-disseminated, diffuse, intrinsic pontine gliomas as measured by progression-free survival and survival distributions.
SECONDARY OBJECTIVES:
- To characterize toxicities associated with R115777 treatment in combination with and post radiation therapy.
II. To characterize radiographic changes in brainstem gliomas treated with radiation and R115777 using MRI, perfusion and diffusion imaging and PET scans.
OUTLINE: This is a phase I (closed to accrual as of 1/19/06), multicenter, dose-escalation study of tipifarnib followed by a phase II safety and efficacy study.
PHASE I: Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses (total of 26 courses) in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of tipifarnib during radiotherapy until the maximum tolerated dose is determined. The MTD is defined as the dose level preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/19/06). Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity.
FOLLOW-UP:
Phase I: Participants contributing only to the phase I part are followed for 90 days after completion of therapy. Adverse events that have not resolved within 90 days after stopping treatment will be followed until resolution.
Phase II: Participants in the phase I part treated at the MTD or participants in the phase II part are followed until the earliest of death or three years after starting treatment.
PROJECTED ACCRUAL: A total of 3-55 patients (3-18 patients for phase I [closed to accrual as of 1/19/06] and a total of 40 patients for phase II [including 6 patients treated in the dose-finding portion of phase I (closed to accrual as of 1/19/06)]) will be accrued for this study within 2.3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (radiation therapy and tipifarnib) | Experimental | Radiation: radiation therapy, Drug: tipifarnibPHASE I: Patients undergo radiotherapy 5 days a week for 6 weeks. Beginning 0-2 days before radiotherapy, patients receive oral tipifarnib twice daily until the completion of radiotherapy. Beginning 2 weeks after the completion of radiotherapy, patients receive oral tipifarnib twice daily in weeks 1-3. Treatment repeats every 4 weeks for up to 24 additional courses (total of 26 courses) in the absence of disease progression or unacceptable toxicity. PHASE II: Patients undergo radiotherapy and receive tipifarnib at the MTD as in phase I (closed to accrual as of 1/19/06). Treatment continues for up to 24 months (26 courses) in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 3 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (17 listed)
- Newly diagnosed non-disseminated intrinsic diffuse brainstem glioma
- Karnofsky performance scale (KPS) (for > 16 yrs of age) or Lansky performance score (LPS) (for =< 16 years of age) => 50 assessed within two weeks prior to registration
- Prior/concurrent therapy:
- Absolute neutrophil count >= 1,000/mm^3
- Platelets >= 100,000/mm^3 (transfusion independent)
Key exclusion criteria (6 listed)
- 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 disseminated intrinsic diffuse brainstem glioma
- Patients taking enzyme-inducing anticonvulsant drugs
- Patients with known allergy to topical or systemic imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole)
- Patients receiving any other anticancer or experimental drug therapy
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 |
|---|---|---|
| radiation therapyAlso: irradiation, radiotherapy, therapy, radiationUndergo radiotherapy | Radiation | Treatment (radiation therapy and tipifarnib) |
| tipifarnibAlso: R115777, ZarnestraGiven orally | Drug | Treatment (radiation therapy and tipifarnib) |
Primary outcome
Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy
Time frame: Day 1 of tipifarnib therapy to week 8
The dose limiting toxicity (DLT) analysis population consists of phase I participants who developed DLT during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without DLTs. DLTs observed during courses 1 and 2 were used to estimate the MTD.
Progression-free Survival (PFS)
Time frame: Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks.
PFS was defined as the interval from initiation of treatment to the earliest of disease progression (tumor increase of 25% over baseline tumor measurement; appearance of new lesion(s); or progressive/worsening neurological status) or death for patients who failed, or to the last date of follow up for patients without failure.
5 secondary outcomes
Change From Baseline in Perfusion Ratio at Two Weeks After Completion of Radiation
Time frame: Baseline and two weeks post completion of radiation
Change From Baseline in Diffusion Ratio at Two Weeks After Completion of Radiation.
Time frame: Baseline and two weeks post completion of radiation
Change From Baseline in Volume FLAIR at Two Weeks After Completion of Radiation
Time frame: Baseline and two weeks post completion of radiation
Mean Tumor to Gray Matter Ratio Measured at Baseline
Time frame: Baseline
Mean Tumor to White Matter Ratio Measured at Baseline
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.
Daphne Haas-Kogan principal investigator
Pediatric Brain Tumor Consortium
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 radiation therapy and tipifarnib in people with Untreated Childhood Brain Stem Glioma, 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 17 inclusion and 6 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 15 May 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 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 24 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?
Number of Participants in the Phase I Component With Dose-limiting Toxicities (DLTs) Observed During the First 8 Weeks (Courses 1 and 2) of Tipifarnib Therapy (time frame: Day 1 of tipifarnib therapy to week 8). 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 15 May 2014.