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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2012-03021 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| PBTC-014 | Other Identifier | Pediatric Brain Tumor Consortium | |
| PBTC-014 | Other Identifier | CTEP | |
| U01CA081457 | U.S. NIH Grant/Contract | View source |
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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)
PRIMARY OBJECTIVES:
I. 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:
I. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| radiation therapy | Radiation | Undergo radiotherapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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)
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
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Daphne Haas-Kogan | Pediatric Brain Tumor Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Pediatric Brain Tumor Consortium | Memphis | Tennessee | 38105 | United States |
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Participants from PBTC member institutions were enrolled on the phase I component between 01/30/2004 and 01/19/2006. The phase II component of the study opened on 06/02/2006 and completed accrual on 12/26/2007.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tipifarnib 100-mg/m2 | Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only. |
| FG001 | Tipifarnib 125-mg/m2 | Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II. |
| FG002 | Tipifarnib 150-mg/m2 | Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tipifarnib 100-mg/m2 | Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Per protocol, participants included phase I participants who developed dose-limiting toxicities during the maximum tolerated dose (MTD) estimation period (courses 1 and 2) or who completed the MTD estimation period (courses 1 and 2) without dose-limiting toxicities. | Posted | Number | Participants | Day 1 of tipifarnib therapy to week 8 |
|
Clinical and laboratory studies to assess adverse events were scheduled pre-treatment, weekly during the first 8 weeks, every 2 weeks for courses 3 -13, and every 12 weeks for courses 14-26. Additional studies were done at the investigator's discretion.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tipifarnib 100-mg/m2 | Tipifarnib 100 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip) | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pediatric Brain Tumor Consortium (James M. Boyett, Ph.D) | Pediatric Brain Tumor Consortium | 901-595-4986 | james.boyett@stjude.org |
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| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D011827 | Radiation |
| C402769 | tipifarnib |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
| D055585 | Physical Phenomena |
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| tipifarnib | Drug | Given orally |
|
|
| 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. | 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. | 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. | 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. | Baseline |
| Non-compliance |
|
| Withdrawal by Subject |
|
| Disease progression |
|
| BG001 | Tipifarnib 125-mg/m2 | Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II. |
| BG002 | Tipifarnib 150-mg/m2 | Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Tipifarnib 125-mg/m2 | Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II. |
| OG002 | Tipifarnib 150-mg/m2 | Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study. |
|
|
| Primary | 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. | Per protocol 40 participants who received at least one dose of tipifarnib were needed for this objective. The analysis population consists of phase I participants treated at the maximum tolerated dose (MTD) and the participants enrolled to the phase II part. | Posted | Median | Full Range | Months | Assessed before the first dose of tipifarnib, every 8 weeks for the first 48 weeks, and then every 12 weeks. |
|
|
|
| Secondary | 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. | The analysis population consists of participants, from both the phase I part and the phase II part, treated at any dose level who had a baseline perfusion ratio value and a second perfusion ratio value measured at approximately 8 weeks after starting treatment. | Posted | Median | Full Range | Ratio | Baseline and two weeks post completion of radiation |
|
|
|
| Secondary | 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. | The analysis population consists of participants, from both the phase I part and the phase II part, treated at any dose level who had a baseline diffusion ratio value and a second diffusion ratio value measured at approximately 8 weeks after starting treatment. | Posted | Median | Full Range | Ratio | Baseline and two weeks post completion of radiation |
|
|
|
| Secondary | 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. | The analysis population consists of participants, from both the phase I part and the phase II part, treated at any dose level who had a baseline volume FLAIR value and a second volume FLAIR value measured at approximately 8 weeks after starting treatment. | Posted | Median | Full Range | cubic centimeters | Baseline and two weeks post completion of radiation |
|
|
|
| Secondary | 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. | The analysis population consists of participants, from both the phase I part and the phase II part, treated at any dose level who had a baseline PET scan. | Posted | Median | Full Range | Ratio | Baseline |
|
|
|
| Secondary | 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. | The analysis population consists of participants, from both the phase I part and the phase II part, treated at any dose level who had a baseline PET scan. | Posted | Median | Full Range | Ratio | Baseline |
|
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|
| 3 |
| 5 |
| 5 |
| 5 |
| EG001 | Tipifarnib 125-mg/m2 | Tipifarnib 125 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. The 125 mg/m2 dose level was determined to be the MTD and therefore the recommended phase II dose. Of the 40 participants treated at this dose level, six were enrolled on the phase I part of the study and 34 were enrolled to the phase II. | 29 | 40 | 40 | 40 |
| EG002 | Tipifarnib 150-mg/m2 | Tipifarnib 150 mg/m2 twice a day for 6 weeks concurrent with radiation therapy followed by a two week rest period. Treatment cycles were 4 weeks (maximum tolerated dose (MTD) estimation period - first 8 weeks). Tipifarnib was continued at 200 mg/m2 twice a day, starting at course 3, for 21 days followed by 7 days of rest. Treatment repeats every 4 weeks for up to 24 additional courses. Local radiation (RT) was initiated 1-2 days following the first dose of tipifarnib and was administered once daily, five days per week , at 180 cGy/day fractions for six weeks to a total dose of 5580 cGy. All participants treated at this dose level were enrolled to the phase I part of the study only. | 3 | 6 | 5 | 6 |
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urticaria (hives, welts, wheals) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, CNS | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, GU | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage/bleeding associated with surgery, intra-operative or postoperative | Surgical and medical procedures | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Blood related |
|
| Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Catheter-related |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Conjunctiva |
|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkalosis (metabolic or respiratory) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bicarbonate, serum-low | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| GGT (gamma-Glutamyl transpeptidase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness, generalized or specific area (not due to neuropathy) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Somnolence/depressed level of consciousness | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ataxia (incoordination) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN VI Lateral deviation of eye |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN X Motor-palate; pharynx, larynx |
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| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN IX Motor-pharynx; Sensory-ear, pharynx, tongue |
|
| Neuropathy: motor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Speech impairment (e.g., dysphasia or aphasia) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Apnea | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Laryngeal nerve dysfunction | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neurology - Other (Specify, __) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN VIII Hearing and balance |
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| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN VII Motor-face; Sensory-taste |
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| Eyelid dysfunction | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Kidney | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Head/Headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Obstruction, GU | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment | Ureter |
|
| Urinary retention (including neurogenic bladder) | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death not associated with CTCAE term | General disorders | CTCAE (3.0) | Systematic Assessment | Disease progression NOS |
|
| Death not associated with CTCAE term | General disorders | CTCAE (3.0) | Systematic Assessment | Death NOS |
|
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Leukocytes (total WBC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight gain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hair loss/alopecia (scalp or body) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pruritus/itching | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bruising (in absence of Grade 3 or 4 thrombocytopenia) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flushing | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cushingoid appearance (e.g., moon face, buffalo hump, centripetal obesity, cutaneous striae) | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis/stomatitis (clinical exam) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, CNS | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, pulmonary/upper respiratory | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | External ear (otitis externa) |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Middle ear (otitis media) |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Mucosa |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Upper airway NOS |
|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-low (hypoglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-high (hypercalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bicarbonate, serum-low | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| GGT (gamma-Glutamyl transpeptidase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-high (hyperkalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bilirubin (hyperbilirubinemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Metabolic/Laboratory - Other (Specify, __) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sodium, serum-high (hypernatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness, generalized or specific area (not due to neuropathy) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment | Left-sided |
|
| Muscle weakness, generalized or specific area (not due to neuropathy) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment | Right-sided |
|
| Ataxia (incoordination) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN VI Lateral deviation of eye |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN VII Motor-face; Sensory-taste |
|
| Neuropathy: motor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Speech impairment (e.g., dysphasia or aphasia) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN X Motor-palate; pharynx, larynx |
|
| Mood alteration - Depression | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN III Pupil, upper eyelid, extra ocular movements |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN IX Motor-pharynx; Sensory-ear, pharynx, tongue |
|
| Neuropathy: sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pyramidal tract dysfunction (e.g., increased tone, hyperreflexia, positive Babinski, decreased fine | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Somnolence/depressed level of consciousness | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN XII Motor-tongue |
|
| Tremor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Personality/behavioral | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration - Agitation | Psychiatric disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN IV Downward, inward movement of eye |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN XI Motor-sternomastoid and trapezius |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN II Vision |
|
| Ophthalmoplegia/diplopia (double vision) | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nystagmus | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision-blurred vision | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Head/headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Abdomen NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Extremity-limb | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Throat/pharynx/larynx | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Back | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Middle ear | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Eye | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Muscle | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary retention (including neurogenic bladder) | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Incontinence, urinary | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Stomach | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gastritis (including bile reflux gastritis) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Heartburn/dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness, generalized or specific area (not due to neuropathy) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment | Lower Extremity |
|
| Ocular surface disease | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision-photophobia | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pulmonary/Upper Respiratory - Other (Specify, __) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | CN V Motor-jaw muscles; Sensory-facial |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Sinusitis NOS |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Urinary tract infection NOS |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Skin infection |
|
| Sweating | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: hand-foot skin reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Febrile neutropenia (fever of unknown origin) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Upper aerodigestive NOS |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Bronchitis NOS |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Bladder (urinary) |
|
| Infection with unknown ANC | Infections and infestations | CTCAE (3.0) | Systematic Assessment | Catheter-related |
|
| Opportunistic infection associated with >=Grade 2 Lymphopenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Extremity-lower (gait/walking) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Extremity-upper (function) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness, generalized or specific area (not due to neuropathy) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Chest/thorax NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - Neck | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hiccoughs (hiccups, singultus) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pneumonitis/pulmonary infiltrates | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided