| ID | Type | Description | Link |
|---|---|---|---|
| NABTC-0108 | |||
| U01CA062399 | U.S. NIH Grant/Contract | View source | |
| CDR0000257267 | Registry Identifier | PDQ (Physician Data Query) |
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Phase II trial to study the effectiveness of imatinib mesylate in treating patients who have recurrent meningioma. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth
PRIMARY OBJECTIVE:
I. Determine the efficacy of imatinib mesylate, in terms of 6-month progression-free survival, of patients with recurrent meningioma.
SECONDARY OBJECTIVES I. Determine the response rate and overall survival of patients treated with this drug.
II. Evaluate the safety profile of this drug in these patients. III. Determine the pharmacokinetics of this drug in these patients. IV. Develop exploratory data concerning surrogate markers of of angiogenic activity in vivo using functional neuro-imaging studies and in vitro assays of serum angiogenic peptides of this drug in these patients.
V. Develop exploratory data concerning evidence of platelet-derived growth factor (PDGF) inhibition in tumor specimens taken from patients undergoing surgery VI. Develop exploratory data correlating molecular abnormalities in the tumor with response in patients treated with this drug.
OUTLINE: This is a multicenter study. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes vs no), histology (benign vs atypical or malignant), neurofibromatosis positivity (yes vs no), and preoperative candidacy (yes vs no).
Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study within 8-12 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment (imatinib mesylate) | Experimental | Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| imatinib mesylate | Drug | Given orally |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 6 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (magnetic resonance imaging [MRI]) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | At 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival According to Response Evaluation Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration |
| Measure | Description | Time Frame |
|---|---|---|
| Determine Surrogate Markers of Angiogenic Peptides Using Functional Neuro-imaging and in Vitro Bioassays | Study terminated early, only 22 patients entered on study. Hence, this secondary outcome was never analyzed due number of patients. | 5 years |
| Evidence of Platelet-derived Growth Factor (PDGF) Inhibition in Tumor Specimens |
Inclusion Criteria:
Histologically confirmed meningioma
Unequivocal evidence of tumor recurrence or progression by MRI or CT scan (on steroid dosage that is stable for at least 5 days)
Evaluable residual disease by MRI or CT scan if previously treated with surgical resection for recurrent or progressive disease
Newly diagnosed recurrent disease that requires surgical debulking allowed
Prior standard external-beam radiotherapy, interstitial brachytherapy, or gamma-knife radiosurgery allowed provided disease has progressed since completion of therapy
Patients with a history of NF may have other stable Central Nervous System (CNS) tumors (e.g., schwannoma, acoustic neuroma, or ependymoma) provided those lesions have been stable in size for the past 6 months
Performance status - Karnofsky 60-100%
More than 8 weeks
Absolute neutrophil count at least 2,000/mm^3
Platelet count at least 120,000/mm^3
Hemoglobin at least 10 g/dL (transfusions allowed)
No bleeding disorders
Bilirubin less than 2 times upper limit of normal (ULN)
Serum glutamic oxaloacetic transaminase (SGOT) less than 2 times ULN
Prothrombin Time (PT), Partial thromboplastin time (PTT), and International normalized Ratio (INR) no greater than 1.5 times ULN
Creatinine less than 1.5 mg/dL
Creatinine clearance at least 60 mL/min
No deep venous or arterial thrombosis within the past 6 weeks
No pulmonary embolism within the past 6 weeks
No serious active infection
No prior intracranial hemorrhage
No concurrent disease that would obscure toxicity or dangerously alter drug metabolism
No other malignancy except nonmelanoma skin cancer or carcinoma in situ of the cervix unless the patient is in complete remission and off all therapy for that disease for at least 3 years
No other significant medical illness that would preclude study participation
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 3 months after study participation
At least 1 week since prior interferon or thalidomide
No concurrent immunotherapy
Concurrent epoetin alfa allowed
At least 4 weeks since prior cytotoxic chemotherapy
At least 2 weeks since prior vincristine
At least 6 weeks since prior nitrosoureas
At least 3 weeks since prior hydroxyurea or procarbazine
No concurrent chemotherapy
At least 1 week since prior tamoxifen
No concurrent hormonal therapy
At least 4 weeks since prior radiotherapy
No concurrent radiotherapy
Recovered from prior surgery
Recovered from all prior therapy
At least 1 week since prior noncytotoxic therapy (e.g., isotretinoin) except radiosensitizers
At least 2 weeks since prior drugs that affect hepatic metabolism
At least 4 weeks since prior investigational agents
No concurrent warfarin (heparin or low-molecular weight heparin allowed)
No other concurrent investigational agents
No concurrent acetaminophen of more than 500 mg/day
No other concurrent anticancer therapy
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Wen, MD | North American Brain Tumor Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California Los Angeles | Los Angeles | California | 90095 | United States | ||
| University of California San Francisco |
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patients enrolled between June 2003 ad August 2005 in an outpatient clinic setting.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment (Imatinib Mesylate) | Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| laboratory biomarker analysis | Other | Correlative studies |
|
| pharmacological study | Other | Correlative studies |
|
|
| 3 years |
| Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 | percentage of patients who had grade 3 or grade 4 adverse events | Up to 5 years after completion of study treatment |
| Tumor Response as Assessed by MRI Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | Up to 5 years |
| Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics) | Blood collected before and at 1,2,4 ad 24 hours after ingestion of imatinib on day 8 of cycle 1 result is the measurement of the before dosing on day 8 (trough level) and the 24 hour dosing day 8 | pre dosing on day 8 and 24 hour dosing day 8 of Pre-dosing Day 9 |
| Determine Survival for Patients Treated With Imatinib Mesylate | survival determined from start of treatment to date of death | 3 years |
insufficient samples to allow Platelet-derived growth factor receptor (PDGFR-alpha and -beta expression to be correlated Of 22 patients only 7 samples available and only 5 yielded adequate tissue |
| - 3 years |
| Determine Correlating Molecular Abnormalities in the Tumor With Response to Treatment | Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over Baseline (BL) if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). | 3 years |
| San Francisco |
| California |
| 94115 |
| United States |
| National Cancer Institute Neuro-Oncology Branch | Bethesda | Maryland | 20814 | United States |
| Dana Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| Memorial Sloan-Kettering Cancer Center | New York | New York | 10021 | United States |
| University of Texas Southwestern Medical Center | Dallas | Texas | 75235 | United States |
| University of Wisconsin | Madison | Wisconsin | 53792 | United States |
| COMPLETED |
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| NOT COMPLETED |
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23 patients were enrolled and evaluated however 1 patient was found to be ineligible as patient had a second malignancy within 3 years of registration. Demographics for this patient are reported.
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| ID | Title | Description |
|---|---|---|
| BG000 | Treatment (Imatinib Mesylate) | Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Karnofsky Performance Status Scale (KPS) | High best 100 normal no complaints no disease 90 capable of normal activity few symptoms/disease 80 normal activity w/ some difficulty some symptoms/signs 70 caring for self not capable of normal activity/work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care/help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures/treatment 10 moribund rapidly progressive fatal disease processes 0 death | Median | Full Range | units on a scale |
| |||||||||||||||||||||
| Histology | using the WHO classification histology code which is the International classification for Oncology Benign (WHO grade I) Atypical (WHO grade II) Anaplastic (WHO grade III) | Number | participants |
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| Prior Surgeries | Median | Full Range | surgeries |
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| Prior Radiation Therapies | Median | Full Range | Radiation Therapies |
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| Prior Chemotherapy Regimens | Median | Full Range | Chemotherapy Regimens |
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| 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 Months - Progression-free Survival According to Response Evaluation Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (magnetic resonance imaging [MRI]) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | Only 19 of the 23 patients were evaluable for response | Posted | Number | percentage of participants | At 6 months |
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| Secondary | Progression-free Survival According to Response Evaluation Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | Of the 22 eligible patients only 19 were evaluable for response | Posted | Median | Full Range | months | 3 years |
| |||||||||||||||||||||||||||
| Secondary | Toxicity as Assessed by the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTC) Version 2.0 | percentage of patients who had grade 3 or grade 4 adverse events | Posted | Number | percentage of patients | Up to 5 years after completion of study treatment |
|
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| Secondary | Tumor Response as Assessed by MRI Using Macdonald Criteria | The Macdonald criteria, roughly similarly to other systems, divides response into 4 types of response based on imaging (MRI) and clinical features 1: complete response; 2: partial response; 3:stable disease; 4:progression Complete response imaging features: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks; no new lesions clinical features; no corticosteroids; clinically stable or improved Partial response imaging features: 50% or more decrease of all measurable enhancing lesions sustained for at least 4 weeks: no new lesions clinical features: stable or reduced corticosteroids; clinically stable or improved Stable disease imaging features: does not qualify for complete response, partial response or progression clinical features: clinically stable Progression imaging features: 25% of more increase in enhancing lesions; any new lesions clinical features: clinical deterioration | response at first scan | Posted | Number | participants | Up to 5 years |
| ||||||||||||||||||||||||||||
| Secondary | Concentration (Steady State) of Imatinib During Cycle One (Pharmacokinetics) | Blood collected before and at 1,2,4 ad 24 hours after ingestion of imatinib on day 8 of cycle 1 result is the measurement of the before dosing on day 8 (trough level) and the 24 hour dosing day 8 | Only 14 samples available / evaluable for analysis | Posted | Mean | Standard Deviation | ng/ml | pre dosing on day 8 and 24 hour dosing day 8 of Pre-dosing Day 9 |
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| Secondary | Determine Survival for Patients Treated With Imatinib Mesylate | survival determined from start of treatment to date of death | death date of 7 patients were unknown at time of analysis | Posted | Median | Full Range | months | 3 years |
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| Other Pre-specified | Determine Surrogate Markers of Angiogenic Peptides Using Functional Neuro-imaging and in Vitro Bioassays | Study terminated early, only 22 patients entered on study. Hence, this secondary outcome was never analyzed due number of patients. | Study terminated early, only 22 patients entered on study. Hence, this secondary outcome was never analyzed due to number of patients. | Posted | 5 years |
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| Other Pre-specified | Evidence of Platelet-derived Growth Factor (PDGF) Inhibition in Tumor Specimens | insufficient samples to allow Platelet-derived growth factor receptor (PDGFR-alpha and -beta expression to be correlated Of 22 patients only 7 samples available and only 5 yielded adequate tissue | insufficient samples to allow PDGFR-alpha and -beta expression to be correlated Of 22 patients only 7 samples available and only 5 yielded adequate tissue | Posted | - 3 years |
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| Other Pre-specified | Determine Correlating Molecular Abnormalities in the Tumor With Response to Treatment | Measurable: Bidimensionally measurable lesions w/ clearly defined margins by MRI Evaluable: Unidimensionally measurable lesions, masses w/margins not clearly defined. Complete Response (CR): Complete disappearance of all measurable/evaluable disease. No new lesions. No evidence of non-evaluable disease. Patients on minimal/no steroids. Partial Response (PR): >/= to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No progression of evaluable disease. Responders must be on same/decreasing doses of dexamethasone. Stable/No Response: Does not qualify for CR, PR, or progression. Progression: 25% increase in the sum of products of all measurable lesions over smallest sum observed (over Baseline (BL) if no decrease), OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). | Study terminated early, only 22 patients entered on study. Hence, this secondary outcome was never analyzed due to number of patients. | Posted | 3 years |
|
3 years
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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 | Treatment (Imatinib Mesylate) | Patients receive oral imatinib mesylate once or twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study/ laboratory biomarker analysis imatinib mesylate: Given orally laboratory biomarker analysis: Correlative studies pharmacological study: Correlative studies | 0 | 22 | 10 | 22 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| anemia | Blood and lymphatic system disorders | CTCAE (2.0) | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | CTCAE (2.0) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | CTCAE (2.0) | Non-systematic Assessment |
| |
| CNS (intracranial) Hemorrhage | Nervous system disorders | CTCAE (2.0) | Non-systematic Assessment |
| |
| dehydrations | Metabolism and nutrition disorders | CTCAE (2.0) | Non-systematic Assessment |
| |
| dizziness | Nervous system disorders | CTCAE (2.0) | Non-systematic Assessment |
| |
| elevated serum glutamic pyruvic transaminase | Investigations | CTCAE (2.0) | Non-systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (2.0) | Non-systematic Assessment |
|
The study was closed prematurely due to limited activity and slow accrual. Study was designed to enroll (statistically powered) for 30 patients into each group (30 benign; 30 Atypical and 30 Anaplastic) meningioma's. Study enroll only 23 patients.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Patrick Wen, MD | Adult Brain Tumor Consortium (ABTC) | 410-955-8837 | jfisher@jhmi.edu |
| ID | Term |
|---|---|
| D008579 | Meningioma |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D009380 | Neoplasms, Nerve Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009383 | Neoplasms, Vascular Tissue |
| D008577 | Meningeal Neoplasms |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009422 | Nervous System Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D000068877 | Imatinib Mesylate |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
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| Anaplastic (WHO grade III) |
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