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| Name | Class |
|---|---|
| Rady Children's Hospital, San Diego | OTHER |
| Duke University | OTHER |
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy together with erlotinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with radiation therapy and to see how well they work in treating young patients with newly diagnosed glioma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a phase I dose-escalation study of erlotinib followed by a phase II study.
Cohorts of patients receive escalating doses of erlotinib until the maximum tolerated dose (MTD) is determined.
PROJECTED ACCRUAL: A total of 75-80 patients (15-20 for the phase I portion and 60 for the phase II portion) will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with High-Grade/Low-Grade Glioma | Experimental | Patients with newly diagnosed high-grade glioma (excluding those originating in the brain stem) and unfavorable low-grade glioma who are ≥ 3 years and <26 years of age. Patients receiving enzyme-inducing anticonvulsants (EIACs) are not eligible for this study. Patients with spinal cord tumors will be eligible for the Phase I and Phase II component of this study, but they will not be taken into consideration to estimate PFS in the Phase II component of this trial because of their notoriously worse prognosis. Patients receive erlotinib hydrochloride. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erlotinib hydrochloride | Drug | This study has 2 components: a Phase I component which estimated the MTD and DLT(s) of erlotinib given once a day during and after conventionally fractionated RT for a period of 8 weeks (DLT-evaluation period), followed by continuous administration of this medication for up to 3 years; and a Phase II component where erlotinib will be given at the MTD during and after RT for 2 years. The recommended dose of erlotinib for the Phase II component of the current study is 120mg/m2 per day (maximum dose of 200mg per day). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Dose-limiting Toxicity (DLT) | DLT was defined as any of the following toxicities attributable to erlotinib therapy: thrombocytopenia grade 3 and 4; neutropenia grade 4; or any grade 3 and 4 non-hematologic toxicity except for grade 3 diarrhea and grade 3 nausea and vomiting lasting ≤48 hours in participants not receiving optimal supportive therapy, grade 3 skin rash, which did not affect normal daily activities, grade 3 fever or nonneutropenic infection, grade 3 seizures, grade 3 weight gain or loss, and grade 3 transaminase elevation that returned to grade 1 or baseline within 7 days. After enrollment of the first 4 participants, grade 3 and 4 electrolyte abnormalities that resolved to ≤grade 2 within 7 days were excluded as DLT. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. | During the first 8 weeks of therapy |
| Maximum Tolerated Dose (MTD) of Erlotinib | MTD was defined as the highest dosage level in which no more than one of six assessable participants experienced dose-limiting toxicities (DLT). The dosage of erlotinib was increased by approximately 30% in each dosage level starting at 80% of the MTD in adults with solid tumors. A traditional 3+3 dose escalation scheme was used to estimate the MTD. | During the first 8 weeks of therapy. |
| Progression Free Survival (PFS) | Progression-free survival (PFS) distributions for the Phase II participants with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were calculated using Kaplan-Meier estimates (n=41). PFS was defined as the interval between treatment start and initial failure, including clinical or radiologic progression or death from any cause. PFS was not calculated for the other disease types. | 1 and 2 years after end of therapy |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax of Erlotinib and Its Metabolite OSI-420 | Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose. | After first dose of therapy, and Day 8 of therapy |
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DISEASE CHARACTERISTICS:
Diagnosis of high-grade glioma of 1 of the following types:
Unfavorable low-grade glioma
Histologically confirmed high-grade glioma (WHO grade III or IV) of 1 of the following subtypes:
Newly diagnosed disease
Intracranial or spinal cord tumors allowed
PATIENT CHARACTERISTICS:
Age
Performance status
Life expectancy
Hematopoietic
Hepatic
Renal
Cardiovascular
Pulmonary
Other
PRIOR CONCURRENT THERAPY:
Biologic therapy
Chemotherapy
Endocrine therapy
Radiotherapy
Surgery
Other
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| Name | Affiliation | Role |
|---|---|---|
| Alberto Broniscer, MD | St. Jude Children's Research Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Diego | San Diego | California | 92123-4282 | United States | ||
| Duke Children's Hospital and Health Center |
Not provided
| Label | URL |
|---|---|
| St. Jude Children's Research Hospital | View source |
| Clinical Trials Open at St. Jude | View source |
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Participants had newly diagnosed high-grade glioma (except those originating in the brain stem) and unfavorable low-grade glioma and were ≥ 3 and ≤21 years of age. Participants receiving enzyme-inducing anticonvulsants (EIACs) were not eligible for this study. Patients with spinal cord tumors were eligible for the Phase II component of this study.
Overall accrual included 62 unique subjects. Five subjects participated in both Phase I and Phase II. Phase I enrolled 23 (03/2005-06/2007). Phase II enrolled an additional 39 participants (08/2007-11/2010) plus 5 carried over from Phase I for a total of 44. One of the 39 accrued to Phase II was enrolled at Rady Children's Hospital.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase I Only | 18 participants were enrolled on the Phase I portion of the trial only. |
| FG001 | Phase I and Phase II | 5 patients participated in both the Phase I portion and the Phase II portion of the study. |
| FG002 | Phase II Only | 39 participants were enrolled on the Phase II portion of the trial only. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase I Only | 18 participants were enrolled on the Phase I portion of the trial only. |
| BG001 | Phase I and Phase II | 5 patients participated in both the Phase I portion and the Phase II portion of the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 With Dose-limiting Toxicity (DLT) | DLT was defined as any of the following toxicities attributable to erlotinib therapy: thrombocytopenia grade 3 and 4; neutropenia grade 4; or any grade 3 and 4 non-hematologic toxicity except for grade 3 diarrhea and grade 3 nausea and vomiting lasting ≤48 hours in participants not receiving optimal supportive therapy, grade 3 skin rash, which did not affect normal daily activities, grade 3 fever or nonneutropenic infection, grade 3 seizures, grade 3 weight gain or loss, and grade 3 transaminase elevation that returned to grade 1 or baseline within 7 days. After enrollment of the first 4 participants, grade 3 and 4 electrolyte abnormalities that resolved to ≤grade 2 within 7 days were excluded as DLT. Toxicities were graded according to the Common Terminology Criteria for Adverse Events version 3.0. | 23 participants were enrolled on Phase I component; 22 were analyzed for DLT over 4 dose levels. 1 treated at dose level 120mg/m^2 was not assessable for DLT due to early tumor progression. 4 were treated before and 19 after the study was amended to exclude grade 3 and 4 electrolyte abnormalities that resolved to ≤ grade 2 within 7 days. | Posted | Number | participants | During the first 8 weeks of therapy |
Adverse events were collected systematically for each of the 23 Phase I and 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy).
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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 | 70 mg/m^2 (Phase I) | Participants received dose of 70 mg/m^2, range of actual dose was 68-83 mg/m^2. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Non-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) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alberto Broniscer, MD | St. Jude Children's Research Hospital | 866-966-5934 | info@stjude.org |
Not provided
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D001254 | Astrocytoma |
| D009837 | Oligodendroglioma |
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| D005910 | Glioma |
| D013120 | Spinal Cord Neoplasms |
| ID | Term |
|---|---|
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000069347 | Erlotinib Hydrochloride |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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|
|
| Erlotinib Tmax | Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose. | After first dose of therapy |
| AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 | Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose. | After first dose of therapy, and Day 8 of therapy |
| Number of Positive Mutations of EGFR and Downstream Pathways | Statistical analyses of genomic changes, expression profiles and validation studies should be considered in an exploratory and hypothesis-generating context. Fresh frozen tumor tissue was obtained at the time of tumor resection and diagnosis. DNA was extracted from formalin-fixed, paraffin-embedded tissue. The entire PTEN coding sequence (exons 1-9), exons 1, 9 and 20 of PIK3CA, and exons 17-24 of EGFR were evaluated using exon-specific PCR amplification, and immunohistochemistry was done. Tumor lesions were considered positive if >25% cells were immunoreactive. | Once at tumor resection and diagnosis |
| Ability of Erlotinib to Inhibit EGFR Signaling | The objective was to test the ability of erlotinib to inhibit the EGFR signaling in patients with high-grade glioma who required a second surgery. This outcome was not assessed due to insufficient availability of tumor and control samples for analysis. | 5 Years |
| Correlation Between Standard Magnetic Resonance Imaging and Investigational Radiologic Techniques in Assessing Tumor Response to This Treatment | This objective was to prospectively investigate the correlation between standard magnetic resonance imaging (MRI) and investigational radiologic techniques (MR spectroscopy, perfusion/diffusion, PET scan, DEMRI/BLAST) in assessing tumor response to this treatment. | at diagnosis and regular intervals during therapy (up to 2 years after start of therapy) |
| To Prospectively Investigate the Technical Factors Involved in Planning and Administering Conformal Fractionated RT as Outlined in This Study, and to Correlate RT Dosimetry With Patterns of Failure, Standard and Investigational Imaging and Toxicity | 5 Years |
| Plasma and CSF Levels of VEGF, bFGF, and SDF1 | This objective was to determine the plasma and CSF levels of the VEGF, bFGF, and SDF1 at diagnosis, and the plasma levels of these factors at regular intervals during therapy, and to analyze the association of these results with tumor response. | at diagnosis and regular intervals during therapy (up to 2 years after start of therapy) |
| Number of Participants Experiencing Grade 3 or 4 Toxicity Events | Adverse events were collected systematically for each of the 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy). | From start of therapy through 2 years. |
| Durham |
| North Carolina |
| 27710 |
| United States |
| St. Jude Children's Research Hospital | Memphis | Tennessee | 38105 | United States |
| Progressive disease |
|
| Intercurrent illness |
|
| BG002 | Phase II Only | 39 participants were enrolled on the Phase II portion of the trial only. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Diagnosis | Number | participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | 70 mg/m^2 | Dose level 1 was 70 mg/m^2, range of actual dosage was 68-83 mg/m^2. |
| OG001 | 90 mg/m^2 | Dose level 2 was 90 mg/m^2, range of actual dosage was 85-87.5 mg/m^2. |
| OG002 | 120 mg/m^2 | Dose level 3 was 120 mg/m^2, range of actual dosage was 107-128 mg/m^2. |
| OG003 | 160 mg/m^2 | Dose level 4 was 160 mg/m^2, range of actual dosage was 151.5-167 mg/m^2. |
|
|
| Secondary | Cmax of Erlotinib and Its Metabolite OSI-420 | Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose. | Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study. | Posted | Median | Full Range | mg/mL | After first dose of therapy, and Day 8 of therapy |
|
|
|
| Secondary | Erlotinib Tmax | Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose. | Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study. | Posted | Median | Full Range | hours | After first dose of therapy |
|
|
|
| Secondary | AUC Time 0-infinite (AUCinf) of Erlotinib and Its Metabolite OSI-420 | Although the calculated dose of erlotinib was rounded to the nearest 25 mg, the actual dosage administered to patients was within 12% of the prescribed dosage in all but 1 patient. The latter patient received erlotinib at the lowest dosage level and the actual dosage was 19% higher than the calculated dose. | Pharmacokinetic variables were obtained in 17 patients enrolled on the Phase I portion of the study. | Posted | Median | Full Range | mg*h/mL | After first dose of therapy, and Day 8 of therapy |
|
|
|
| Secondary | Number of Positive Mutations of EGFR and Downstream Pathways | Statistical analyses of genomic changes, expression profiles and validation studies should be considered in an exploratory and hypothesis-generating context. Fresh frozen tumor tissue was obtained at the time of tumor resection and diagnosis. DNA was extracted from formalin-fixed, paraffin-embedded tissue. The entire PTEN coding sequence (exons 1-9), exons 1, 9 and 20 of PIK3CA, and exons 17-24 of EGFR were evaluated using exon-specific PCR amplification, and immunohistochemistry was done. Tumor lesions were considered positive if >25% cells were immunoreactive. | Unstained slides were available for immunohistochemistry analysis in 21 of the 23 Phase I participants. | Posted | Number | participants | Once at tumor resection and diagnosis |
|
|
|
| Primary | Maximum Tolerated Dose (MTD) of Erlotinib | MTD was defined as the highest dosage level in which no more than one of six assessable participants experienced dose-limiting toxicities (DLT). The dosage of erlotinib was increased by approximately 30% in each dosage level starting at 80% of the MTD in adults with solid tumors. A traditional 3+3 dose escalation scheme was used to estimate the MTD. | 22 participants were analyzed for MTD over 4 dose levels. One of 23 enrolled participants was not evaluable due to early disease progression. | Posted | Number | mg/m^2 | During the first 8 weeks of therapy. |
|
|
|
| Primary | Progression Free Survival (PFS) | Progression-free survival (PFS) distributions for the Phase II participants with anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) were calculated using Kaplan-Meier estimates (n=41). PFS was defined as the interval between treatment start and initial failure, including clinical or radiologic progression or death from any cause. PFS was not calculated for the other disease types. | Per protocol, 41 participants with either anaplastic astrocytoma or glioblastoma multiforme were analyzed for this outcome. | Posted | Mean | Standard Deviation | years | 1 and 2 years after end of therapy |
|
|
|
|
| Secondary | Ability of Erlotinib to Inhibit EGFR Signaling | The objective was to test the ability of erlotinib to inhibit the EGFR signaling in patients with high-grade glioma who required a second surgery. This outcome was not assessed due to insufficient availability of tumor and control samples for analysis. | This outcome was not assessed due to insufficient availability of tumor and control samples for analysis. | Posted | 5 Years |
|
|
| Secondary | Correlation Between Standard Magnetic Resonance Imaging and Investigational Radiologic Techniques in Assessing Tumor Response to This Treatment | This objective was to prospectively investigate the correlation between standard magnetic resonance imaging (MRI) and investigational radiologic techniques (MR spectroscopy, perfusion/diffusion, PET scan, DEMRI/BLAST) in assessing tumor response to this treatment. | This objective became obsolete over the course of the protocol, and data was not collected. | Posted | at diagnosis and regular intervals during therapy (up to 2 years after start of therapy) |
|
|
| Secondary | To Prospectively Investigate the Technical Factors Involved in Planning and Administering Conformal Fractionated RT as Outlined in This Study, and to Correlate RT Dosimetry With Patterns of Failure, Standard and Investigational Imaging and Toxicity | This objective became obsolete over the course of the protocol, and data was not collected. | Posted | 5 Years |
|
|
| Secondary | Plasma and CSF Levels of VEGF, bFGF, and SDF1 | This objective was to determine the plasma and CSF levels of the VEGF, bFGF, and SDF1 at diagnosis, and the plasma levels of these factors at regular intervals during therapy, and to analyze the association of these results with tumor response. | This objective became obsolete over the course of the protocol, and data was not collected. | Posted | at diagnosis and regular intervals during therapy (up to 2 years after start of therapy) |
|
|
| Secondary | Number of Participants Experiencing Grade 3 or 4 Toxicity Events | Adverse events were collected systematically for each of the 44 Phase II participants from the time of enrollment to the completion of therapy (approximately 2 years from start of therapy). | All 44 Phase II participants were evaluated. Eight of 16 participants with lymphopenia received dexamethasone within 4 weeks of the recorded toxicity. In both participants with headache, there was a documented progressive disease within 3 days of the recorded headache. | Posted | Number | Participants | From start of therapy through 2 years. |
|
|
|
| 4 |
| 7 |
| 7 |
| 7 |
| EG001 | 90 mg/m^2 (Phase I) | Participants received dose of 90 mg/m^2, range of actual dose was 85-87.5 mg/m^2. | 1 | 3 | 3 | 3 |
| EG002 | 120 mg/m^2 (Phase I) | Participants received dose of 120 mg/m^2, range of actual dose was 107-128 mg/m^2. | 2 | 7 | 7 | 7 |
| EG003 | 160 mg/m^2 (Phase I) | Participants received dose of 160 mg/m^2, range of actual dose was 151.5-167 mg/m^2. | 4 | 6 | 6 | 6 |
| EG004 | Phase II | Phase II participants received 120 mg/m^2. | 26 | 44 | 43 | 44 |
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment | Eight of the 16 patients with lymphopenia received dexamethasone within 4 weeks of the recorded toxicity. |
|
| Neutrophils | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pruritis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash/Desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash/Acne | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| ALT/AST | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bilirubin | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Headache | General disorders | CTCAE (3.0) | Systematic Assessment | There was a documented progressive disease within 3 days of the recorded headache. |
|
| Lipase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hearing: patients wihtout baseline audiogram and not enrolled in a monitoring program | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Otitis, external ear (non-infectious) | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Leukocytes (total WBC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils/granulocytes (ANC/AGC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Supraventricular and nodal arrhythmia, sinus tachycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever (in absence of neutrophenia defined as ANC <1.0 x 10e9/L) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Insomnia | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Chelitis | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dermatology/Skin - other | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry skin | 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 |
|
| Hyperpigmentation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nail changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pruritus/itching | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Striae | 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 |
|
| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gastrointestinal - Other | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Heartburn/dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis/stomatitis (clinical exam), oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis/stomatitis (functional/symptomatic), oral cavity | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Taste alteration (dysgeusia) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, pulmonary/upper respiratory, nose | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection - Other | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neurophils, external ear (otitis externa) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, middle ear (otitis media) | Infections and infestations | CTCAE (3.0) | Non-systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, upper airway NOS | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Opportunistic infection associated with >=Grade 2 lymphopenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Edema: limb | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| AST, SGOT (serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bicarbonate, serum-low | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bilirubin (hyperbilirubinemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-low (hypoglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Musculoskeletal/soft tissue - other | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ataxia (incoordination) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration, anxiety | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration, depression | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neurology - other | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| 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 |
|
| Tremor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nystagmus | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ocular/visual - other | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ophthalmoplegia/diplopia (double vision) | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision-blurred vision | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain - other | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, abdomen NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, back | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, head/headache | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, throat/pharynx/larynx | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-high (hyperkalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sodium, serum-high (hypernatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Auditory/Ear - other | Ear and labyrinth disorders | CTCAE (3.0) | Non-systematic Assessment |
|
| Otitis, middle ear (non-infectious | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rigors/chills | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flushing | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: hand-foot skin reaction | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ulceration | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dental: teeth | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, CNS | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage, GU, urinary NOS | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, Anal/perianal | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, eye NOS | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, mucosa | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, pharynx | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, sinus | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, skin (cellulitis) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, urinary tract NOS | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, wound | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-high (hypercalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Extremity-lower (gait/walking) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cognitive disturbance | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Personality/behavioral | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Somnolence/depressed level of consciousness | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Syncope (fainting) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ocular surface disease | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vision-photophobia | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, chest/thorax NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, external ear | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, eye | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, joint | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nasal cavity/paranasal sinus reactions | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary retention (including neurogenic bladder) | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, lip/perioral | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Allergic reaction/hypersensitivity (including drug fever) | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Supraventricular and nodal arrhythmia, sinus bradycardia | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight gain | General 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 |
|
| Burn | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Rash: dermatitis associated with radiation, radiation | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Death not associated with CTCAE term, disease progression NOS | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment | Death occurred due to a sledding accident. Participant had completed all therapy and was in follow-up. |
|
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gastritis (including bile reflex gastritis) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Ulcer, GI, stomach | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hepatobiliary/pancreas - other | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, conjunctiva | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, dental-tooth | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, Foreign body | Infections and infestations | CTCAE (3.0) | Systematic Assessment | e.g., graft, implant, prosthesis, stent |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, lung (pnemonia) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, meninges (meningitis) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, nose | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, oral cavity-gums (gingivitis) | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Infection with normal ANC or Grade 1 or 2 neutrophils, rectum | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Amylase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cholesterol, serum-high (hypercholestremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lipase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Metabolic/laboratory - other | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Muscle weakness, generalized or specific area (not due to neuropathy), whole body/generalized | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Trismus (difficulty, restriction or pain when opening mouth) | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Leak, cerebrospinal fluid (CSF) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mood alteration, agitation | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial, CN VI Lateral deviation of eye | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial, CN VII motor-face: sensory-taste | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: cranial, CN VIII hearing and balance | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Psychosis (hallucinations/delusions) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pyramidal tract dysfunction | Nervous system disorders | CTCAE (3.0) | Systematic Assessment | (e.g., increased tone, hyperreflexia, positive Babinski, decreased motor coordination) |
|
| Cataract | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry eye syndrome | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Eyelid dysfunction | Eye disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bronchospasm, wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pulmonary/upper respiratory - other | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cystitis | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Secondary malignancy - possibly related to cancer treatment | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (3.0) | Systematic Assessment |
|
| Sexual/reproductive function - other | Reproductive system and breast disorders | CTCAE (3.0) | Systematic Assessment |
|
| Intra-operative injury, brain | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Flu-like syndrome | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, extremity-limb | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, muscle | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, oral cavity | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, pain NOS | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain, stomach | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lymphatics - other | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D018302 |
| Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| Erlotinib, Day 8 of therapy |
|
| OSI-420, after first dose of therapy |
|
| OSI-420, Day 8 of therapy |
|
| Erlotinib, Day 8 of therapy |
|
| Erlotinib, Day 8 of therapy |
|
| OSI-420, after first dose of therapy |
|
| OSI-420, Day 8 of therapy |
|
| Title | Measurements |
|---|---|
|
| 2-year PFS |
|
| Kaplan-Meier |
| 0.33 |
| Standard Error of the Mean |
| 0.12 |
| 2-Sided |
| 95 |
| 0.09 |
| 0.57 |
| No |
| Superiority or Other |
| 1-year progression free survival (n=20) | Kaplan-Meier | 0.45 | Standard Deviation | 0.106 | 2-Sided | 95 | 0.198 | 0.602 | No | Superiority or Other |
| 2-year progression free survival (n=20) | Kaplan-Meier | 0.150 | Standard Deviation | 0.069 | 2-Sided | 95 | 0.015 | 0.285 | No | Superiority or Other |
| 1-year progression free survival (n=21) | Kaplan-Meier | 0.190 | Standard Deviation | 0.077 | 2-Sided | 95 | 0.039 | 0.341 | No | Superiority or Other |
| 2-year progression free survival (n=21) | Kaplan-Meier | 0.190 | Standard Deviation | 0.077 | 2-Sided | 95 | 0.039 | 0.341 | No | Superiority or Other |
| Blood: Neutrophils |
|
| Blood: Platelets |
|
| Dermatologic: Pruritus |
|
| Dermatologic: Rash/Desquamation |
|
| Dermatologic: Rash/acne |
|
| Gastrointestinal: Anorexia |
|
| Gastrointestinal: Diarrhea |
|
| Gastrointestinal: Dysphagia |
|
| Gastrointestinal: Mucositis |
|
| Gastrointestinal: Nausea |
|
| Gastrointestinal: Vomiting |
|
| Metabolic: ALT/AST |
|
| Metabolic: Hypokalemia |
|
| Metabolic: Bilirubin |
|
| Pain: Headache |
|
| Constitutional: Fatigue |
|
| Constitutional: Weight Loss |
|