Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Subjects are asked to take part in a clinical research study that tests Eribulin, a new drug. Eribulin is an investigational (experimental) anti-cancer agent that has not been approved by the Food and Drug Administration (FDA) for use in patients with brain metastases. Eribulin is FDA approved for use in patients with metastatic breast cancer but the effect it may or may not have on brain metastases has not been studied.
Primary Objectives:
To determine the 3-month central nervous system (CNS)-progression free survival (PFS) for patients with metastatic breast cancer with brain metastases treated with eribulin mesylate.
Secondary Objective(s):
1. Estimate CNS complete and partial response rates (CR and PR) and duration of CNS response in this patient population.
2 Evaluate toxicity in patients with breast cancer with brain metastases treated with eribulin mesylate.
3 Estimate clinical benefit rate (CBR) at 3 months in breast cancer patients with brain metastases treated with eribulin mesylate. (CBR is the sum of CR, PR and stable disease at 3 months).
4 To estimate systemic disease (extra cranial) response rate and duration of systemic response in this patient population.
5 Overall survival in this patient population.
Design:
This is a phase II study that will require patients to evaluate the primary objective (CNS PFS at 3 months). Study patients will have a baseline brain MRI and a second MRI at 12 weeks to evaluate disease.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eribulin Mesylate | Experimental | The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eribulin Mesylate | Drug | Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS) | The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. | At 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (RR) | The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. | up to 2 years from start of treatment |
| Median Duration of CNS Response |
Not provided
Inclusion Criteria:
Female with histologically confirmed breast cancer.
Patients must have evidence of metastatic disease (non measurable disease is eligible).
Radiologically confirmed metastatic brain lesion by MRI.
Brain metastases from breast cancer with or without prior WBRT, STS of surgical resection. Progression must be documented in an at least one lesion untreated by SRS or in any site after surgery or WBRT.
Patients must be neurologically stable and with stable dose steroids and anticonvulsants for at least 1 week prior to obtaining the baseline MRI of the brain, and/or at least 1 week prior to beginning study treatment.
No presence of uncontrolled systemic disease or tumor related complication which, in opinion of the investigator, might restrict life expectancy to less than 3 months.
Patients may not be on any cytotoxic chemotherapy or hormonal treatment for breast cancer during protocol treatment. Trastuzumab is allowed in HER2 positive patients).
Able to comprehend and willing to sign an Informed Consent Form (ICF)
Karnofsky performance status ≥ 60
No brain radiation therapy > 4 weeks
No chemotherapy for > 3 weeks before planned start of protocol treatment
Adequate bone marrow, renal, and hepatic function, per local reference laboratory ranges as follows:
Females of child-bearing potential must have a negative pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy (double barrier method of birth control or abstinence) from screening through 3 months after the last dose of treatment
Able to undergo MRI evaluation with and without gadolinium contrast
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Paula Silverman, MD | University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland | Ohio | 44106 | United States |
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Eribulin Mesylate | The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Participants who were put on study
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Eribulin Mesylate | The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS) | The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. | Posted | Number | 95% Confidence Interval | percentage of participants | At 12 weeks |
|
30 days after treatment has been discontinued, an average of 5 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Eribulin Mesylate | The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE v4.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE v4.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paula Silverman | Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | 1-800-641-2422 | CTUreferral@UHhospitals.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 25, 2018 | Jan 16, 2020 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C490954 | eribulin |
| D008279 | Magnetic Resonance Imaging |
| ID | Term |
|---|---|
| D014054 | Tomography |
| D003952 | Diagnostic Imaging |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| MRI | Device | An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate |
|
|
| Pre-Medication: Zofran | Drug | Zofran at 8mg orally. Given at the discretion of the treating physician |
|
| Pre-Medication: Decadron | Drug | decadron at 8mg orally. Given at the discretion of the treating physician |
|
The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. |
| up to 2 years from start of treatment |
| Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events | The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin. | up to 2 years from start of treatment |
| Number of Patients With CBR | The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR) | At 12 weeks |
| Systemic Disease Response Rate | The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population | up to 2 years from start of treatment |
| Median Overall Survival (OS) | The study team will generate a Kaplan-Meier curve of OS. | up to 2 years from start of treatment |
| Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Cleveland | Ohio | 44195 | United States |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Objective Response Rate (RR) | The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. | Posted | Number | percentage of participants | up to 2 years from start of treatment |
|
|
|
| Secondary | Median Duration of CNS Response | The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria. | Posted | Median | Full Range | weeks | up to 2 years from start of treatment |
|
|
|
| Secondary | Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events | The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin. | Posted | Count of Participants | Participants | up to 2 years from start of treatment |
|
|
|
| Secondary | Number of Patients With CBR | The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR) | Posted | Count of Participants | Participants | At 12 weeks |
|
|
|
| Secondary | Systemic Disease Response Rate | The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population | Data not collected due to too few participants on study for a significant length of time | Posted | up to 2 years from start of treatment |
|
|
| Secondary | Median Overall Survival (OS) | The study team will generate a Kaplan-Meier curve of OS. | Posted | Median | Full Range | months | up to 2 years from start of treatment |
|
|
|
| 7 |
| 9 |
| 3 |
| 9 |
| 9 |
| 9 |
| Fatigue | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| worsening pseudomeningeocele | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Blurred vision | Eye disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dry eye | Eye disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Aura | Eye disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Neuro; Other- perception/focus | Eye disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Vision Change | Eye disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Mucositis oral | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Edema face | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Edema limbs | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Fever | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Gait disturbance | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Malaise | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Non-cardiac chest pain | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Pain | General disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Lung infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
|
| Rhinitis infective | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE v4.0 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Chest wall pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Joint range motion decreased | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Lock jaw | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Ataxia | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| L carpel tunnel | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| woozy feeling | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Oculomotor nerve disorder | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Recurrent laryngeal nerve palsy | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Chronic kidney disease | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Urinary urgency | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| folliculitis | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Lymphedema | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Thromboembolic event | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | CTCAE v4.0 | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D017437 |
| Skin and Connective Tissue Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |