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| ID | Type | Description | Link |
|---|---|---|---|
| CLBH589BUS38T | Other Grant/Funding Number | Novartis | |
| 2010-0050 | Other Identifier | Institutional Review Board | |
| 2014-1298 | Other Identifier | Institutional Review Board | |
| A534260 | Other Identifier | UW Madison | |
| SMPH\MEDICINE\HEM-ONC | Other Identifier | UW Madison | |
| NCI-2011-00320 | Registry Identifier | NCI Trial ID |
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Study did not meet statistical requirements to continue.
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| Name | Class |
|---|---|
| Novartis Pharmaceuticals | INDUSTRY |
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This summary will use Panobinostat (LBH589) in patients with neuroendocrine tumors to see how the patient's tumor responds to panobinostat. Additionally, this study will examine how long it takes neuroendocrine tumor patient's cancer to progress while taking the drug and examine the overall survival of patients using panobinostat. Also, the study will examine the toxicity and tolerability of panobinostat in the patient population. Finally, this study will look at the effect of panobinostat on Notch 1 signaling before and after treatment with panobinostat.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| panobinostat | Experimental | This is a single arm trial. All patients will take panobinostat |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| panobinostat (LBH589) | Drug | Panobinostat will be taken once daily at 20 mg three times a week (every Monday, Wednesday, Friday). It will be taken as long as patients are benefiting from treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Confirmed anti-tumor response rate will be validated by the Response Evaluation Criteria in Solid Tumors (RECIST). All participants included in the study will be assessed for response to the proposed panobinostat treatment, even if there are protocol treatment deviations. Each participant will be assigned one of the following categories: complete response, partial response, stable disease, progressive disease, early death from malignant disease, early death from toxicity, early death because of other cause, or unknown. | every 8 weeks, up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Toxicities | Evaluate the toxicity and tolerability of panobinostat in the patient population | up to 5 years |
| Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Noelle LoConte, MD | University of Wisconsin, Madison | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Wisconsin, Madison | Madison | Wisconsin | 53792 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27261467 | Derived | Jin N, Lubner SJ, Mulkerin DL, Rajguru S, Carmichael L, Chen H, Holen KD, LoConte NK. A Phase II Trial of a Histone Deacetylase Inhibitor Panobinostat in Patients With Low-Grade Neuroendocrine Tumors. Oncologist. 2016 Jul;21(7):785-6. doi: 10.1634/theoncologist.2016-0060. Epub 2016 Jun 3. |
| Label | URL |
|---|---|
| University of Wisconsin Carbone Cancer Center | View source |
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This study actively recruited from April 2010 through May 2011 at a large cancer center in Wisconsin.
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| ID | Title | Description |
|---|---|---|
| FG000 | Panobinostat | Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Panobinostat | Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Number |
| 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 | Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. | Confirmed anti-tumor response rate will be validated by the Response Evaluation Criteria in Solid Tumors (RECIST). All participants included in the study will be assessed for response to the proposed panobinostat treatment, even if there are protocol treatment deviations. Each participant will be assigned one of the following categories: complete response, partial response, stable disease, progressive disease, early death from malignant disease, early death from toxicity, early death because of other cause, or unknown. | Posted | Number | participants | every 8 weeks, up to 5 years |
|
Adverse events were collected for 5 years.
Grade refers to the severity of the Adverse Event (AE) from grades 1 through 5, where 1 is a mild AE, and 5 is death related to an adverse AE.
Systematic Adverse Event assessment included regular assessment of subjects by the treating investigator, including physical exam, ECOG performance status, ECG, and lab assessments.
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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 | Panobinostat | Adult patients with histologically confirmed, metastatic, low-grade NETs and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 were treated with oral panobinostat 20 mg once daily three times per week. Treatment was continued until patients experienced unacceptable toxicities or disease progression. The study was stopped at planned interim analysis based on a Simon two-stage design. Fifteen patients were accrued, and 13 were evaluable for response. No responses were seen, but the stable disease rate was 100%. The median progression-free survival (PFS) was 9.9 months, and the median overall survival was 47.3 months. Fatigue (27%), thrombocytopenia (20%), diarrhea (13%), and nausea (13%) were the most common related grade 3 toxicities. There was one grade 4 thrombocytopenia (7%). These results did not meet the prespecified criteria to open the study to full accrual. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Grade 3 albumin, serum low | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
This study was terminated early because of the use of objective response rate as the primary outcome measure, which is a shortcoming of this study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Noelle LoConte | University of Wisconsin Carbone Cancer Center | 608-265-5883 | ns3@medicine.wisc.edu |
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| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| ID | Term |
|---|---|
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077767 | Panobinostat |
| ID | Term |
|---|---|
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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| Up to 5 years |
| Delineate the Expression of Notch 1 in Neuroendocrine Tumor Samples Before and During Treatment With Panobinostat | The expression of Notch 1 in neuroendocrine tumor samples will be evaluated prior to Cycle 1 Day 1 dose and at the end of Cycle 2 of treatment of treatment. | Pre-treatment and up to week 12 |
| Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | Up to 5 years |
| 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 | Number of Participants With Toxicities | Evaluate the toxicity and tolerability of panobinostat in the patient population | Posted | Number | participants | up to 5 years |
|
|
|
| Secondary | Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | Posted | Median | 90% Confidence Interval | months | Up to 5 years |
|
|
|
| Secondary | Delineate the Expression of Notch 1 in Neuroendocrine Tumor Samples Before and During Treatment With Panobinostat | The expression of Notch 1 in neuroendocrine tumor samples will be evaluated prior to Cycle 1 Day 1 dose and at the end of Cycle 2 of treatment of treatment. | Data to delineate the expression of Notch 1 in neuroendocrine tumor samples was not collected. The question regarding the role of Notch1 in well-differentiated NET remains unanswered. | Posted | Pre-treatment and up to week 12 |
|
|
| Secondary | Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat | Posted | Median | 90% Confidence Interval | months | Up to 5 years |
|
|
|
| 6 |
| 15 |
| 15 |
| 15 |
| Grade 1 creatinine | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 febrile neutropenia | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Grade 1 glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 2 hemoglobin | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 hypotension | Cardiac disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 5 hypotension (death) | Cardiac disorders | CTCAE (3.0) | Systematic Assessment | Subject expired less than 30 days off study |
|
| Grade 3 infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 lipase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 4 lipase | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 1 magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 4 pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 2 pancreatitis | Hepatobiliary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 4 platelets (thrombocytopenia) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 Pneumotosis Coli | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 1 potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 3 small bowel NOS | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Grade 1 sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Alkaline phosphatase | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Allergic rhinitis | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Allergy/Immunology | Immune system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| AST, SGOT(serum glutamic oxaloacetic transaminase) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Auditory/Ear | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Bruising (in absence of Grade 3 or 4 thrombocytopenia) | Injury, poisoning and procedural complications | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-high (hypercalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cervical spine-range of motion | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cholesterol, serum-high (hypercholesteremia) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Creatinine | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dermatology/Skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Edema: limb | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Elevated Triglycerides | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Flushing | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gastritis (including bile reflux gastritis) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Gastrointestinal | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| GGT (gamma-Glutamyl transpeptidase) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Gingivitis | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| Glomerular filtration rate | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hair loss/alopecia (scalp or body) | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Heartburn/dyspepsia | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemoglobin | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Hemorrhage/Bleeding | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Infection | Infections and infestations | CTCAE (3.0) | Systematic Assessment |
|
| INR (International Normalized Ratio of prothrombin time) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Joint-function | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Leukocytes (total WBC) | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Lipase | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-high (hypermagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Magnesium, serum-low (hypomagnesemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Mucositis/stomatitis (clinical exam) - Oral cavity | Gastrointestinal 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 |
|
| Musculoskeletal/Soft Tissue | Musculoskeletal and connective tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nail changes | Skin and subcutaneous tissue disorders | CTCAE (3.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neuropathy: sensory | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Neutrophils/granulocytes (ANC/AGC) | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Phosphate, serum-low (hypophosphatemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-high (hyperkalemia) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Potassium, serum-low (hypokalemia) | Investigations | CTCAE (3.0) | Systematic Assessment |
|
| Rash/desquamation | Skin and subcutaneous tissue 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 |
|
| Sweating (diaphoresis) | General disorders | CTCAE (3.0) | Systematic Assessment |
|
| Taste alteration (dysgeusia) | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombosis/thrombus/embolism | Vascular disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thrombotic microangiopathy | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thyroid function, high (hyperthyroidism, thyrotoxicosis) | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
|
| Thyroid function, low (hypothyroidism) | Endocrine disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | CTCAE (3.0) | Systematic Assessment |
|
| Tremor | Nervous system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Triglyceride, serum-high (hypertriglyceridemia) | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Urinary frequency/urgency | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (3.0) | Systematic Assessment |
|
| Weight loss | Investigations | CTCAE (3.0) | Systematic Assessment |
|
Not provided
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| D009380 | Neoplasms, Nerve Tissue |
| D006880 |
| Hydroxy Acids |
| D002264 | Carboxylic Acids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |