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| ID | Type | Description | Link |
|---|---|---|---|
| BIBF 1199.94 | Other Identifier | Boehringer-Ingleheim |
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| Name | Class |
|---|---|
| Boehringer Ingelheim | INDUSTRY |
| Wake Forest University Health Sciences | OTHER |
| University of Virginia | OTHER |
| Massachusetts General Hospital |
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BIBF 1120 is a newly discovered compound that may stop cancer cells from growing abnormally. This drug is currently being used in treatment for other cancers in research studies and information from those other research studies suggests that this agent, BIBF 1120, may help to stop recurrent malignant glioma cells from multiplying and it may also prevent the growth of new blood vessels at the site of the tumor. In this research study, the investigators are looking to see how well BIBF 1120 works in patients with recurrent malignant gliomas.
This is a two arm, multicenter, open label phase II trial in adult patients with recurrent supratentorial high-grade glioma. One arm (the "bevacizumab naïve" arm) will enroll patients who have not received prior bevacizumab therapy, and the other arm (the "post-bevacizumab" arm) will enroll patients who have experienced progression on bevacizumab.
All subjects will receive BIBF 1120 at 200mg orally, twice daily in cycles of 28 days. Subjects will come to the clinic on Day 1 of each cycle (or within 2 days prior) for blood and urine tests and a physical and neurologic exam. Bloods will also be checked within 2 days before or after Day 15 of Cycles 1 and 2. An additional blood sample will be taken on Days 1 and 8 of Cycle 1, at the start of every even-numbered cycle, and at the end of active study treatment. Subjects will have gadolinium-enhanced brain MRI scans performed with tumor measurements at screening, at the start of even-numbered cycles, and at the end of active study treatment(unless already obtained within 4 weeks of completing study treatment). 40 study subjects will have diffusion- and perfusion-weighted MRI at baseline, after 1 week on therapy (± 2 days), within 2 days prior to the start of every even-numbered cycle, and at the end of treatment (unless already obtained within 4 weeks of completing study treatment).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Bevacizumab Naive | Experimental | Bevacizumab naive subjects |
|
| Prior Bevacizumab | Experimental | Patients previously treated with bevacizumab |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIBF 1120 | Drug | 200 mg BID oral for 28 day cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| 6-Month Progression Free Survival | To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6). | Six months |
| 3-Month Progression Free Survival | To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3). | 3 months |
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response | Best radiographic response in both populations. There were no participants with partial or complete responses, so the results are being reported in the proportion of participants who experienced stable disease (SD) as their best response (as opposed to progressive disease). | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Exploratory Objective #1: Progression-free Survival at 3- and 6-months for Participants With Recurrent Anaplastic Gliomas (AG) | To explore the efficacy of BIBF 1120 in bevacizumab-naïve and bevacizumab-treated participants with recurrent anaplastic gliomas (AG) survival was assessed at 6 months for Arm A and 3 months for Arm B. | Arm A - 6 months; Arm B - 3 months |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Y Wen, M.D. | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Dana-Farber Cancer Institute |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25338318 | Derived | Norden AD, Schiff D, Ahluwalia MS, Lesser GJ, Nayak L, Lee EQ, Rinne ML, Muzikansky A, Dietrich J, Purow B, Doherty LM, LaFrankie DC, Pulverenti JR, Rifenburg JA, Ruland SF, Smith KH, Gaffey SC, McCluskey C, Ligon KL, Reardon DA, Wen PY. Phase II trial of triple tyrosine kinase receptor inhibitor nintedanib in recurrent high-grade gliomas. J Neurooncol. 2015 Jan;121(2):297-302. doi: 10.1007/s11060-014-1631-y. Epub 2014 Oct 22. |
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Study activated at Dana-Farber Cancer Institute in May 2012 and was eventually activated at Massachusetts General Hospital, Cleveland Clinic, and University of Virginia. The bevacizumab-treated arm closed to accrual in December 2012 and the bevacizumab-naive arm closed in March 2013, both due to futility.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (Bevacizumab-naive) - GBM | Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was glioblastoma (GBM). |
| FG001 | Arm A (Bevacizumab-naive) - AG | Participants who had not been treated with bevacizumab prior to entering the study, and whose current histology was anaplastic glioma (AG). |
| FG002 | Arm B (Bevacizumab Treated) - GBM | Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was glioblastoma (GBM). |
| FG003 | Arm B (Bevacizumab Treated) - AG | Participants who had been previously treated with bevacizumab prior to entering the study, and whose currently histology was anaplastic glioma (AG). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
One participant from Arm B (GBM) was removed from analysis, aside from the review of adverse events, due to later determining she did not meet eligibility requirements as a result of prior stereotatic radiosurgery received prior to starting the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A Bevacizumab-naive | Bevacizumab-naive participants |
| BG001 | Arm B Bevacizumab-treated | Bevacizumab-treated participants |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| 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 | 6-Month Progression Free Survival | To determine the efficacy of BIBF 1120 in bevacizumab-naive participants with recurrent glioblastoma (GBM) as measured by 6-month progression-free survival (PFS6). | Posted | Number | percentage of participants | Six months |
|
|
Adverse events were collected on each participant from the time the informed consent document was signed up until 30 days after the last dose of study drug.
Abnormal laboratory values or diagnostic tests results constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic tests.
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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 | Arm A | Bevacizumab-naive participants |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3 possibly related to BIBF 1120, expected |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
The trial intended to enroll 14 participants onto Arm A GBM, but only 10 enrolled due to futility. In addition, 10 AG participants were to be enrolled onto each Arm as exploratory cohorts, but again due to futility only 4 enrolled onto Arm B.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patrick Y. Wen, MD | Dana-Farber Cancer Institute | 6176322166 | pwen@partners.org |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| D018316 | Gliosarcoma |
| D001254 | Astrocytoma |
| D009837 | Oligodendroglioma |
| D001932 | Brain Neoplasms |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
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| ID | Term |
|---|---|
| C530716 | nintedanib |
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| OTHER |
| The Cleveland Clinic | OTHER |
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| Overall Survival | Overall survival in both populations | 2 years |
| Time-to-tumor Progression | Time-to-tumor progression in both populations. | 2 years |
| Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) | Safety profile in both populations - as adverse events are posted separately in detail, these results will demonstrate serious adverse events (defined as grades 3-5) that were judged at least possibly related to Nintedanib (BIBF 1120). | 2 years |
| Exploratory Objective #2: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Tumor Genotype and/or Expression Profile | To explore the extent to which the tumor's genotype and expression profile correlate with outcome. | 2 years |
| Exploratory Objective #3: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Serum Angiogenic Peptides, Circulating Endothelial Cells, and/or Circulating Progenitor Cells | To explore the correlation between serum angiogenic peptides, circulating endothelial cells, and circulating progenitor cells with response to therapy. | 2 years |
| Exploratory Objective #4: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Perfusion MRI, Diffusion MRI | To explore the correlation between perfusion MRI, diffusion MRI and response to therapy. | 2 years |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Cleveland Clinic | Cleveland | Ohio | 44195 | United States |
| University of Virginia | Charlottesville | Virginia | 22908-4324 | United States |
| Death |
|
| Lack of Efficacy |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Karnofsky Performance Status | Karnofsky Performance Status ranges from 0 (Dead) to 100 (Normal, no complaints, no evidence of disease) in increments of 10. This was measured at baseline, prior to any treatment on study. | Median | Full Range | Units on a scale |
|
|
| Primary | 3-Month Progression Free Survival | To determine the efficacy of BIBF 1120 in bevacizumab-treated participants with recurrent GBM as measured by 3-month progression free survival (PFS3). | Posted | Number | percentage of participants | 3 months |
|
|
|
| Secondary | Proportion of Participants Experiencing Stable Disease (SD) as Their Best Radiographic Response | Best radiographic response in both populations. There were no participants with partial or complete responses, so the results are being reported in the proportion of participants who experienced stable disease (SD) as their best response (as opposed to progressive disease). | Posted | Number | % of patients with best response SD | 2 years |
|
|
|
| Secondary | Overall Survival | Overall survival in both populations | Posted | Median | 95% Confidence Interval | months | 2 years |
|
|
|
| Secondary | Time-to-tumor Progression | Time-to-tumor progression in both populations. | Posted | Median | 95% Confidence Interval | days | 2 years |
|
|
|
| Secondary | Safety Profile as Summarized With Descriptive Statistics (Using Toxicity Data Gathered on Trial) | Safety profile in both populations - as adverse events are posted separately in detail, these results will demonstrate serious adverse events (defined as grades 3-5) that were judged at least possibly related to Nintedanib (BIBF 1120). | Posted | Number | number of incidents | 2 years |
|
|
|
| Other Pre-specified | Exploratory Objective #1: Progression-free Survival at 3- and 6-months for Participants With Recurrent Anaplastic Gliomas (AG) | To explore the efficacy of BIBF 1120 in bevacizumab-naïve and bevacizumab-treated participants with recurrent anaplastic gliomas (AG) survival was assessed at 6 months for Arm A and 3 months for Arm B. | Posted | Number | percentage of participants | Arm A - 6 months; Arm B - 3 months |
|
|
|
| Other Pre-specified | Exploratory Objective #2: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Tumor Genotype and/or Expression Profile | To explore the extent to which the tumor's genotype and expression profile correlate with outcome. | Not Posted | 2 years |
| Other Pre-specified | Exploratory Objective #3: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Serum Angiogenic Peptides, Circulating Endothelial Cells, and/or Circulating Progenitor Cells | To explore the correlation between serum angiogenic peptides, circulating endothelial cells, and circulating progenitor cells with response to therapy. | Not Posted | 2 years |
| Other Pre-specified | Exploratory Objective #4: Determination if Any Correlation Exists Between Patient Outcomes (Survival, PFS3, PFS6) and Perfusion MRI, Diffusion MRI | To explore the correlation between perfusion MRI, diffusion MRI and response to therapy. | Not Posted | 2 years |
| 8 |
| 22 |
| 22 |
| 22 |
| EG001 | Arm B | Bevacizumab-treated participants | 5 | 14 | 14 | 14 |
|
| Agitation | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 4, unrelated to BIBF 1120, unexpected |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment | Grade 3, possibly related to BIBF 1120, expected |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment | Grade 3, possibly related to BIBF 1120, expected |
|
| Colonic perforation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Same participant - grade 4, possibly related to BIBF 1120 and unexpected; grade 5, possibly related to BIBF 1120 and expected. |
|
| Death NOS | General disorders | CTCAE (4.0) | Non-systematic Assessment | Arm A - grade 5, unrelated, unexpected Arm B - both events grade 5, unrelated, unexpected |
|
| Delirium | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3, unlikely related to BIBF 1120, unexpected |
|
| Depression | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 4, unrelated to BIBF 1120, unexpected |
|
| Dysphasia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 2, possibly related to BIBF 1120, unexpected |
|
| Edema cerebral | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Arm A - grade 4, unlikely related to BIBF 1120, unexpected Arm B - grade <4, unrelated to BIBF 1120, unexpected |
|
| Enterocolitis | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3, unrelated to BIBF 1120, unexpected Grade 5, unrelated to BIBF 1120, unexpected |
|
| Hydrocephalus | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3, unrelated to BIBF 1120, unexpected |
|
| Intracranial hemorrhage | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment | Same participant - grade 2 and grade 3, possibly related to BIBF 1120, unexpected |
|
| Muscle weakness left-sided | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 2, unrelated to BIBF 1120, unexpected |
|
| Muscle weakness right-sided | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 2, possibly related to BIBF 1120, unexpected |
|
| Suicidal ideation | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment | Same participant - grade 2 twice, unrelated to BIBF 1120, and unexpected |
|
| Suicidal attempt | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment | Grade 3, unrelated to BIBF 1120, unexpected |
|
| Thromboembolic event | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment | Arm A - grade 5, possibly related to BIBF 1120, unexpected Arm B - grade 3, unlikely related to BIBF 1120, unexpected |
|
| Vascular disorders - Other | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment | Both grade 4, one unlikely related and other unrelated to BIBF 1120, both unexpected |
|
| Agitation | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dysarthria | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Eye disorders - Other | Eye disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Personality change | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Weight loss | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Activated partial thromboplastic time prolonged | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Ataxia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cardiac disorders - Other | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Concentration impairment | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Cushingoid | Endocrine disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Delirium | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Duodenal hemorrhage | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Dysphasia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Encephalopathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Infusion site extravasation | General disorders | CTCAE (4.0) | Non-systematic Assessment |
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| INR increased | Investigations | CTCAE (4.0) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Lung infection | Infections and infestations | CTCAE (4.0) | Non-systematic Assessment |
|
| Muscle weakness left-sided | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Muscle weakness right-sided | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Peripheral motor neuropathy | Nervous system disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Purpura | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Respiratory, thoracic and mediastinal disorders - Other | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Vaginal hemorrhage | Reproductive system and breast disorders | CTCAE (4.0) | Non-systematic Assessment |
|
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| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Hypophosphatemia |
|
| Intracranial hemorrhage |
|
| Colonic perforation |
|
| Pulmonary embolism |
|