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Trial record 46 of 138 for:    lbh-589

Treatment of Resistant Metastatic Melanoma Using Decitabine, Temozolomide and Panobinostat

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ClinicalTrials.gov Identifier: NCT00925132
Recruitment Status : Terminated (Change in the number of approved drugs for metastatic melanoma)
First Posted : June 19, 2009
Results First Posted : July 2, 2017
Last Update Posted : July 2, 2017
Sponsor:
Collaborators:
Holden Comprehensive Cancer Center
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Mohammed M Milhem, University of Iowa

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Metastatic Melanoma
Intervention Drug: Temozolomide, Decitabine, Panobinostat
Enrollment 39

Recruitment Details Subjects were recruited between December 2009 through June 2015. The study population was accessed via the Principal Investigator's medical clinic at Holden Comprehensive Cancer Center.
Pre-assignment Details Following consent, all subjects undergo screening procedures to verify eligibility for participation in the study. Screening included physical exam, blood and urine tests to check general health, blood test for fetal hemoglobin, blood test for pregnancy (only for women of childbearing age), ECG and Echo, CT and FDG-PET, and tumor measurements
Arm/Group Title Phase I:Decitabine 0.1mg/kg + Panobinostat 10mg + Temozolomide Phase I:Decitabine 0.1 mg/kg + Panobinostat 20mg +Temozolomide Phase I:Decitabine 0.2 mg/kg + Panobinostat 20mg+Temozolomide Phase I:Decitabine 0.2 mg/kg + Panobinostat 30mg +Temozolomide Phase II:Decitabine 0.2 mg/kg+Panobinostat 30mg+Temozolomide
Hide Arm/Group Description Cohort 1: Participants were administered Decitabine 0.1 mg/kg via subcutaneous injection (SQ) 3x weekly, Panobinostat 10mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1. Cohort 2: Participants were administered Decitabine 0.1 mg/kg via subcutaneous injection (SQ) 3x weekly, Panobinostat 20mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1. Cohort 3: Participants were administered Decitabine 0.2 mg/kg via subcutaneous injection (SQ) 3x weekly, Panobinostat 20mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1. Cohort 4: Participants were administered Decitabine 0.2 mg/kg via subcutaneous injection (SQ) 3x weekly and Panobinostat 30mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1. Participants were administered Decitabine 0.2 mg/kg via subcutaneous injection (SQ) 3x weekly and Panobinostat 30mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1.
Period Title: Overall Study
Started 5 4 4 4 22
Completed 3 4 4 4 17
Not Completed 2 0 0 0 5
Reason Not Completed
Withdrawal by Subject             2             0             0             0             1
Removed due to disease progression             0             0             0             0             4
Arm/Group Title Temozolomide, Decitabine, Panobinostat
Hide Arm/Group Description

Temozolomide - given each cycle.

Decitabine - 6 cohorts with dose escalation.

Panobinostat - 6 cohorts with dose escalation.

Temozolomide, Decitabine, Panobinostat: Temozolomide - given each cycle.

Decitabine - 6 cohorts with dose escalation.

Panobinostat - 6 cohorts with dose escalation.

Overall Number of Baseline Participants 39
Hide Baseline Analysis Population Description
Patients with the diagnosis of metastatic melanoma from any site. These include untreated patients or those treated with chemotherapy or biochemotherapy.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
<=18 years
0
   0.0%
Between 18 and 65 years
25
  64.1%
>=65 years
14
  35.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 participants
Female
16
  41.0%
Male
23
  59.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 39 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
37
  94.9%
More than one race
0
   0.0%
Unknown or Not Reported
2
   5.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 39 participants
39
1.Primary Outcome
Title Phase I - Number of Participants With Dose Limiting Toxicities (DLTs) at a Given Dose Level
Hide Description

A DLT was any Grade 4 toxicity for neutrophils or platelets for ≥ 7 days, Grade 3 toxicity for neutrophils for ≥ 21 days, any Grade 3 solid organ toxicity not explainable by another cause (e.g. neurotoxicity, GI toxicity), metabolic/laboratory toxicity (≥10 x ULN AST) for ≥ 14 days, any Grade 4 infection or QTcF> 500msec EKG. DLTs were assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0.

All adverse events were collected and graded to determine DLTs as assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0. DLTs were assessed to determine the recommended Decitabine and Panobinostat dose for the Phase II portion of the trial.

Time Frame 6 weeks (one full cycle)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients within the 4 dosing cohorts evaluable for DLTs following administration of one full cycle
Arm/Group Title Phase I Dose Escalation
Hide Arm/Group Description:

Temozolomide - given each cycle.

Decitabine - 6 cohorts with dose escalation.

Panobinostat - 6 cohorts with dose escalation.

Overall Number of Participants Analyzed 15
Measure Type: Count of Participants
Unit of Measure: Participants
Cohort 1: Experienced DLT
0
   0.0%
Cohort 2: Experienced DLT
0
   0.0%
Cohort 3: Experienced DLT
0
   0.0%
Cohort 4: Experienced DLT
0
   0.0%
2.Primary Outcome
Title Phase 2 -Number of Patients With a Decrease in Tumor Size Using RECIST and CHOI's Criteria
Hide Description

Tumor response rate was assessed using RECIST criteria in which a complete response was the disappearance of all target lesions; Partial response was a 30% decrease in the sum of the longest dimension (LD) of target lesions, relative to baseline measurement; Progressive disease was an increase of 20% or more in the sum of the LD of target lesions; and Stable disease was a decrease in tumor size of less than 30% or increase of less than 20%.

Tumor response rate was also assessed using CHOI's criteria in which a response was a 10% decrease in tumor size or a 15% decrease in tumor density on contrast-enhanced computed tomography scan.

Tumor response rates were assessed in order to determine effectiveness of the treatment regimen which was defined by the response rate of at least 30% as measured by either the RECIST or Choi’s criteria, and ineffective if the rate is less than 15% on both.

Time Frame 12 weeks (2 cycles)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of patients evaluable for tumor response assessment following 2 cycles of treatment
Arm/Group Title Phase II:Decitabine 0.2 mg/kg +Panobinostat 30mg +Temozolomide
Hide Arm/Group Description:
Participants were administered Decitabine 0.2 mg/kg via subcutaneous injection (SQ) 3x weekly, Panobinostat 30mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1.
Overall Number of Participants Analyzed 17
Measure Type: Count of Participants
Unit of Measure: Participants
Progressive Disease (PD)
12
  70.6%
Stable Disease (SD)
5
  29.4%
3.Secondary Outcome
Title Phase 2 - Number of Participants With Disease Progression
Hide Description Number of participants who died or had disease progression
Time Frame 5 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number patients who received study drug in Phase II portion of trial
Arm/Group Title Phase II:Decitabine 0.2 mg/kg +Panobinostat 30mg+Temozolomide
Hide Arm/Group Description:
Participants were administered Decitabine 0.2 mg/kg via subcutaneous injection (SQ) 3x weekly and Panobinostat 30mg orally (PO) once every 96 hours for 2 weeks and Temozolomide at a dose of 150 mg/m2 orally Day 9 through 13 for 5 doses. Dose for Temozolomide was escalated to 200 mg/m2 for 5 days after Cycle 1.
Overall Number of Participants Analyzed 22
Measure Type: Count of Participants
Unit of Measure: Participants
Died within 5 year time frame
17
  77.3%
Removed due to disease progression
5
  22.7%
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Temozolomide, Decitabine, Panobinostat
Hide Arm/Group Description

Temozolomide - given each cycle.

Decitabine - 6 cohorts with dose escalation.

Panobinostat - 6 cohorts with dose escalation.

Temozolomide, Decitabine, Panobinostat: Temozolomide - given each cycle.

Decitabine - 6 cohorts with dose escalation.

Panobinostat - 6 cohorts with dose escalation.

All-Cause Mortality
Temozolomide, Decitabine, Panobinostat
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Temozolomide, Decitabine, Panobinostat
Affected / at Risk (%) # Events
Total   5/39 (12.82%)    
Gastrointestinal disorders   
Obstruction, GI (small bowel)   1/39 (2.56%)  1
Nervous system disorders   
Syncope   1/39 (2.56%)  1
Renal and urinary disorders   
Obstruction, GU (ureter)   1/39 (2.56%)  1
Respiratory, thoracic and mediastinal disorders   
Pleural Effusion   1/39 (2.56%)  1
Vascular disorders   
Edema-lower extremity   1/39 (2.56%)  1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Temozolomide, Decitabine, Panobinostat
Affected / at Risk (%) # Events
Total   39/39 (100.00%)    
Blood and lymphatic system disorders   
Leukocytes   24/39 (61.54%)  24
Lymphopenia   29/39 (74.36%)  29
RBC Decreased   2/39 (5.13%)  2
Hemoglobin   14/39 (35.90%)  14
Neutrophils   27/39 (69.23%)  27
Platelets   24/39 (61.54%)  24
Coagulation PTT   1/39 (2.56%)  1
Cardiac disorders   
Tachycardia   3/39 (7.69%)  3
Gastrointestinal disorders   
Anorexia   13/39 (33.33%)  13
Constipation   9/39 (23.08%)  9
Nausea   22/39 (56.41%)  22
Vomiting   11/39 (28.21%)  11
Gastrointestinal pain   6/39 (15.38%)  6
Taste alteration (dysgeusia)   1/39 (2.56%)  1
Diarrhea   6/39 (15.38%)  6
Gastritis   1/39 (2.56%)  1
General disorders   
Fatigue   24/39 (61.54%)  24
Fever   3/39 (7.69%)  3
Headache   3/39 (7.69%)  3
Failure to thrive   1/39 (2.56%)  1
Confusion   2/39 (5.13%)  2
Neuropathy   2/39 (5.13%)  2
Insomnia   1/39 (2.56%)  1
Speech impairment   1/39 (2.56%)  1
Dizziness   1/39 (2.56%)  1
Somnolence   2/39 (5.13%)  2
Flu-like symptoms   1/39 (2.56%)  1
Metabolism and nutrition disorders   
ALT   11/39 (28.21%)  11
Albumin   1/39 (2.56%)  1
Bicarbonate-Serum low   4/39 (10.26%)  4
Bilirubin   2/39 (5.13%)  2
Creatinine   3/39 (7.69%)  3
GGT   2/39 (5.13%)  2
Hyperglycemia   14/39 (35.90%)  14
Chloride decreased   1/39 (2.56%)  1
Alkaline Phosphatase   8/39 (20.51%)  8
Hyponatremia   10/39 (25.64%)  10
Albumin-Serum low (hypoalbuminemia)   7/39 (17.95%)  7
Potassium-Serum low (hypokalemia)   6/39 (15.38%)  6
Phosphorous   11/39 (28.21%)  11
Weight Loss   3/39 (7.69%)  3
Calcium, serum-low (hypocalcemia)   6/39 (15.38%)  6
Musculoskeletal and connective tissue disorders   
Musculoskeletal joint pain   1/39 (2.56%)  1
Back pain   1/39 (2.56%)  1
General pain: chest and body   2/39 (5.13%)  2
Nervous system disorders   
Left Sided Weakness   1/39 (2.56%)  1
Anxiety   2/39 (5.13%)  2
Respiratory, thoracic and mediastinal disorders   
Cough   2/39 (5.13%)  2
Dyspnea   1/39 (2.56%)  1
Indicates events were collected by systematic assessment
This study was closed to enrollment early as there was a change in the number of approved drugs for metastatic melanoma, making Temozolomide as a chemotherapy agent, an unlikely treatment for metastatic melanoma.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Mohammed Milhem
Organization: University of Iowa
Phone: 319-356-2324
Responsible Party: Mohammed M Milhem, University of Iowa
ClinicalTrials.gov Identifier: NCT00925132     History of Changes
Other Study ID Numbers: 200807728
First Submitted: June 18, 2009
First Posted: June 19, 2009
Results First Submitted: February 15, 2017
Results First Posted: July 2, 2017
Last Update Posted: July 2, 2017