ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 60 of 138 for:    lbh-589

Study of Panobinostat in Patients With Neuroendocrine Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00985946
Recruitment Status : Terminated (Study did not meet statistical requirements to continue.)
First Posted : September 29, 2009
Results First Posted : July 17, 2017
Last Update Posted : July 17, 2017
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University of Wisconsin, Madison

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neuroendocrine Tumors
Intervention Drug: panobinostat (LBH589)
Enrollment 15

Recruitment Details This study actively recruited from April 2010 through May 2011 at a large cancer center in Wisconsin.
Pre-assignment Details  
Arm/Group Title Panobinostat
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 15 [1]
Completed 8
Not Completed 7
Reason Not Completed
Lost to Follow-up             6
Withdrawal by Subject             1
[1]
Eighty-seven percent (n=13) were evaluable for response.
Arm/Group Title Panobinostat
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants
40-49 years of age 3
50-59 years of age 5
60-69 years of age 4
70-79 years of age 2
>= 80 years of age 1
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
5
  33.3%
Male
10
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
13
  86.7%
Unknown or Not Reported
2
  13.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
0
   0.0%
White
15
 100.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants
15
1.Primary Outcome
Title Tumor Response Rate of Patients With Gastrointestinal Neuroendocrine Tumors Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
Hide Description 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.
Time Frame every 8 weeks, up to 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Panobinostat
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: participants
Stable Disease 15
Complete Response 0
Partial Response 0
Progressive Disease 0
Early death from malignant disease 0
Early death from toxicity 0
Early death because of other cause 0
Unknown 0
2.Secondary Outcome
Title Number of Participants With Toxicities
Hide Description Evaluate the toxicity and tolerability of panobinostat in the patient population
Time Frame up to 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Panobinostat
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Measure Type: Number
Unit of Measure: participants
5
3.Secondary Outcome
Title Evaluate the Time to Progression for Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat
Hide Description [Not Specified]
Time Frame Up to 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Panobinostat
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Median (90% Confidence Interval)
Unit of Measure: months
9.9
(4.1 to 16.9)
4.Secondary Outcome
Title Delineate the Expression of Notch 1 in Neuroendocrine Tumor Samples Before and During Treatment With Panobinostat
Hide Description 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.
Time Frame Pre-treatment and up to week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Panobinostat
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Evaluate the Overall Survival of Patients With Gastrointestinal Neuroendocrine Tumors Treated With Panobinostat
Hide Description [Not Specified]
Time Frame Up to 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Panobinostat
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 15
Median (90% Confidence Interval)
Unit of Measure: months
47.27 [1] 
(17.87 to NA)
[1]
Not reached.
Time Frame Adverse events were collected for 5 years.
Adverse Event Reporting Description

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.

 
Arm/Group Title Panobinostat
Hide Arm/Group Description 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.
All-Cause Mortality
Panobinostat
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Panobinostat
Affected / at Risk (%) # Events
Total   6/15 (40.00%)    
Blood and lymphatic system disorders   
Grade 2 hemoglobin  1  1/15 (6.67%)  1
Grade 4 platelets (thrombocytopenia)  1  1/15 (6.67%)  1
Cardiac disorders   
Grade 3 hypotension  1  1/15 (6.67%)  1
Grade 5 hypotension (death)  1 [1]  1/15 (6.67%)  1
Gastrointestinal disorders   
Grade 3 diarrhea  1  2/15 (13.33%)  2
Grade 3 Pneumotosis Coli  1  1/15 (6.67%)  1
Grade 3 small bowel NOS  1  1/15 (6.67%)  1
General disorders   
Grade 3 pain  1  2/15 (13.33%)  2
Grade 4 pain  1  1/15 (6.67%)  1
Hepatobiliary disorders   
Grade 2 pancreatitis  1  1/15 (6.67%)  1
Infections and infestations   
Grade 3 febrile neutropenia  1  1/15 (6.67%)  1
Grade 3 infection  1  1/15 (6.67%)  1
Metabolism and nutrition disorders   
Grade 3 albumin, serum low  1  1/15 (6.67%)  1
Grade 1 creatinine  1  1/15 (6.67%)  1
Grade 1 glucose, serum-high (hyperglycemia)  1  1/15 (6.67%)  1
Grade 3 lipase  1  1/15 (6.67%)  1
Grade 4 lipase  1  1/15 (6.67%)  1
Grade 1 magnesium, serum-low (hypomagnesemia)  1  1/15 (6.67%)  1
Grade 1 potassium, serum-low (hypokalemia)  1  1/15 (6.67%)  1
Grade 1 sodium, serum-low (hyponatremia)  1  1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Subject expired less than 30 days off study
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Panobinostat
Affected / at Risk (%) # Events
Total   15/15 (100.00%)    
Blood and lymphatic system disorders   
Edema: limb  1  2/15 (13.33%)  3
Hemorrhage/Bleeding  1  1/15 (6.67%)  1
Leukocytes (total WBC)  1  3/15 (20.00%)  18
Lymphopenia  1  3/15 (20.00%)  8
Platelets  1  13/15 (86.67%)  73
Thrombotic microangiopathy  1  1/15 (6.67%)  1
Ear and labyrinth disorders   
Auditory/Ear  1  1/15 (6.67%)  1
Tinnitus  1  1/15 (6.67%)  1
Endocrine disorders   
Thyroid function, high (hyperthyroidism, thyrotoxicosis)  1  4/15 (26.67%)  6
Thyroid function, low (hypothyroidism)  1  8/15 (53.33%)  26
Gastrointestinal disorders   
Anorexia  1  6/15 (40.00%)  18
Constipation  1  1/15 (6.67%)  1
Diarrhea  1  13/15 (86.67%)  52
Dysphagia (difficulty swallowing)  1  1/15 (6.67%)  1
Flatulence  1  4/15 (26.67%)  9
Gastritis (including bile reflux gastritis)  1  1/15 (6.67%)  2
Gastrointestinal  1  3/15 (20.00%)  3
Heartburn/dyspepsia  1  2/15 (13.33%)  2
Mucositis/stomatitis (clinical exam) - Oral cavity  1  3/15 (20.00%)  3
Nausea  1  13/15 (86.67%)  39
Taste alteration (dysgeusia)  1  4/15 (26.67%)  5
Vomiting  1  8/15 (53.33%)  17
General disorders   
Fatigue (asthenia, lethargy, malaise)  1  15/15 (100.00%)  68
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)  1  1/15 (6.67%)  1
Pain  1  11/15 (73.33%)  40
Sweating (diaphoresis)  1  1/15 (6.67%)  1
Immune system disorders   
Allergic rhinitis  1  1/15 (6.67%)  1
Allergy/Immunology  1  1/15 (6.67%)  1
Infections and infestations   
Gingivitis  1  1/15 (6.67%)  1
Infection  1  2/15 (13.33%)  3
Injury, poisoning and procedural complications   
Bruising (in absence of Grade 3 or 4 thrombocytopenia)  1  3/15 (20.00%)  6
Investigations   
Alkaline phosphatase  1  8/15 (53.33%)  15
AST, SGOT(serum glutamic oxaloacetic transaminase)  1  1/15 (6.67%)  1
Cholesterol, serum-high (hypercholesteremia)  1  5/15 (33.33%)  26
Creatinine  1  8/15 (53.33%)  43
GGT (gamma-Glutamyl transpeptidase)  1  8/15 (53.33%)  21
Hemoglobin  1  10/15 (66.67%)  42
INR (International Normalized Ratio of prothrombin time)  1  2/15 (13.33%)  9
Lipase  1  1/15 (6.67%)  1
Potassium, serum-high (hyperkalemia)  1  3/15 (20.00%)  9
Potassium, serum-low (hypokalemia)  1  1/15 (6.67%)  1
Weight loss  1  9/15 (60.00%)  37
Metabolism and nutrition disorders   
Albumin, serum-low (hypoalbuminemia)  1  8/15 (53.33%)  27
Calcium, serum-high (hypercalcemia)  1  1/15 (6.67%)  1
Calcium, serum-low (hypocalcemia)  1  2/15 (13.33%)  4
Dehydration  1  4/15 (26.67%)  4
Elevated Triglycerides  1  1/15 (6.67%)  1
Glucose, serum-high (hyperglycemia)  1  13/15 (86.67%)  61
Magnesium, serum-high (hypermagnesemia)  1  4/15 (26.67%)  8
Magnesium, serum-low (hypomagnesemia)  1  1/15 (6.67%)  1
Phosphate, serum-low (hypophosphatemia)  1  2/15 (13.33%)  8
Sodium, serum-high (hypernatremia)  1  1/15 (6.67%)  1
Sodium, serum-low (hyponatremia)  1  5/15 (33.33%)  18
Triglyceride, serum-high (hypertriglyceridemia)  1  8/15 (53.33%)  51
Musculoskeletal and connective tissue disorders   
Cervical spine-range of motion  1  1/15 (6.67%)  1
Joint-function  1  1/15 (6.67%)  1
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized  1  2/15 (13.33%)  3
Musculoskeletal/Soft Tissue  1  1/15 (6.67%)  1
Nervous system disorders   
Memory impairment  1  1/15 (6.67%)  1
Neuropathy: sensory  1  2/15 (13.33%)  8
Neutrophils/granulocytes (ANC/AGC)  1  4/15 (26.67%)  16
Tremor  1  1/15 (6.67%)  4
Renal and urinary disorders   
Glomerular filtration rate  1  5/15 (33.33%)  12
Urinary frequency/urgency  1  1/15 (6.67%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/15 (6.67%)  1
Dyspnea (shortness of breath)  1  3/15 (20.00%)  4
Skin and subcutaneous tissue disorders   
Dermatology/Skin  1  2/15 (13.33%)  2
Dry skin  1  2/15 (13.33%)  3
Hair loss/alopecia (scalp or body)  1  1/15 (6.67%)  1
Nail changes  1  2/15 (13.33%)  3
Rash/desquamation  1  1/15 (6.67%)  1
Vascular disorders   
Flushing  1  5/15 (33.33%)  20
Hypertension  1  2/15 (13.33%)  3
Hypotension  1  3/15 (20.00%)  5
Thrombosis/thrombus/embolism  1  1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Noelle LoConte
Organization: University of Wisconsin Carbone Cancer Center
Phone: 608-265-5883
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00985946     History of Changes
Other Study ID Numbers: 2010-0050 (CO08209)
CLBH589BUS38T
First Submitted: September 25, 2009
First Posted: September 29, 2009
Results First Submitted: March 17, 2017
Results First Posted: July 17, 2017
Last Update Posted: July 17, 2017