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Trial record 29 of 180 for:    RET

Ponatinib for Advanced Medullary Thyroid Cancer

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: NCT01838642
Recruitment Status : Terminated (Recruiting halted prematurely and will not resume. New study to open soon.)
First Posted : April 24, 2013
Results First Posted : March 17, 2016
Last Update Posted : February 15, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
James Gulley, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Thyroid Neoplasms
Intervention Drug: Ponatinib
Enrollment 3
Recruitment Details  
Pre-assignment Details No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants.
Hide Arm/Group Description

Rearranged during transfection (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Period Title: Overall Study
Started 3
Completed 2
Not Completed 1
Reason Not Completed
Died on study             1
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description

Rearranged during transfection (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Baseline Participants 3
Hide Baseline Analysis Population Description
No participants were enrolled in the RET mutation negative group; study closed prematurely.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
<=18 years
0
   0.0%
Between 18 and 65 years
3
 100.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants
59.13  (5.83)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Female
2
  66.7%
Male
1
  33.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
3
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 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
3
 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 3 participants
3
1.Primary Outcome
Title Overall Response Rate.
Hide Description Defined as the percentage of participants with a best response (complete response (CR) + partial response (PR)) recorded from the start of the treatment until disease progression/recurrence assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Time Frame 2-4 months
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: percentage of participants
Complete Response 0
Partial Response 0
2.Secondary Outcome
Title Progression Free Survival
Hide Description Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame 2-4 months
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 3
Mean (Full Range)
Unit of Measure: months
3.01
(2.07 to 4.13)
3.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame 17 months and 19 days
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: participants
3
4.Secondary Outcome
Title Molecular Differences in Advanced Medullary Thyroid Cancer (MTC)
Hide Description Compare the molecular profile of tumor deoxyribonucleic acid (DNA) prior to treatment with the molecular profile at the time of progression. Prior to the first dose of ponatinib and at time of progression, subjects were to undergo a biopsy of the primary tumor or any metastatic site for analysis of tumor DNA for rearranged during transfection (RET) or rat sarcoma (RAS) mutation. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) and is defined as at least a 20% decrease in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Time Frame Prior to the first dose of ponatinib
Hide Outcome Measure Data
Hide Analysis Population Description
Although molecular profiling was to be completed prior to first dose of ponatinib and at time of progression, samples were tested on arrival only as mutational status was an eligibility requirement. No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: participants
RET mutation 3
RAS mutation 0
5.Secondary Outcome
Title Changes in Serum Levels of MTC Tumor Markers Calcitonin (CTN) and Its Relation With Clinical Response
Hide Description Responders are those subjects with a best biomarker response of complete response (CR) or partial response (PR) and who achieve a clinical response of CR or PR assessed by the following criteria. Biomarker: complete response (CR) is normalization (</= upper limit of normal (ULN)) of CTN (i.e., normal <10 pg/mL) following treatment, confirmed with a repeat CTN level at least 4 weeks apart. Partial response (PR) is a >/=50% decrease in the CTN level relative to baseline level, confirmed with a repeat CTN level at least 4 weeks apart. Clinical: complete response (CR) is an average of 0-2 formed stools per day for a period of at least 4 weeks. Partial response (PR) is a >50% decrease in the average stool frequency relative to baseline and a change in stool consistency from watery to loose (partially formed) for a period of at least 4 weeks.
Time Frame Baseline to 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
None of the participants achieved a clinical response and no data were collected for this assessment. No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Objective Response to Ponatinib
Hide Description Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (Whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Stable disease (SD) is neither shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time Frame up to 4 cycles of treatment with ponatinib
Hide Outcome Measure Data
Hide Analysis Population Description
One participant died on study during cycle 2. No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 2
Measure Type: Number
Unit of Measure: participants
Complete Response (CR) 0
Partial Response (PR) 0
Progressive Disease (PD) 2
Stable Disease (SD) 0
7.Secondary Outcome
Title Changes in Serum Levels of MTC Tumor Markers Carcinoemybryonic Antigen (CEA) and Its Relation With Clinical Response
Hide Description Responders are those subjects with a best biomarker response of complete response (CR) or partial response (PR) and who achieve a clinical response of CR or PR assessed by the following criteria. Biomarker: complete response (CR) is normalization (</= upper limit of normal (ULN)) of CTN (i.e., normal 0-2.5 mcg/L) following treatment, confirmed with a repeat CEA level at least 4 weeks apart. Partial response (PR) is a >/=50% decrease in the CEA level relative to baseline level, confirmed with a repeat CEA level at least 4 weeks apart. Clinical: complete response (CR) is an average of 0-2 formed stools per day for a period of at least 4 weeks. Partial response (PR) is a >50% decrease in the average stool frequency relative to baseline and a change in stool consistency from watery to loose (partially formed) for a period of at least 4 weeks.
Time Frame Baseline to 4 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
None of the participants achieved a clinical response and no data were collected for this assessment. No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Overall Survival
Hide Description Overall survival is defined as the time between the first day of treatment to the day of disease progression.
Time Frame up to 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
No participants were enrolled in the RET mutation negative group; study closed prematurely.
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description:

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

Overall Number of Participants Analyzed 3
Mean (Full Range)
Unit of Measure: months
4.7
(2.1 to 6)
Time Frame 17 months and 19 days
Adverse Event Reporting Description No participants were enrolled in the RET mutation negative group; study closed prematurely.
 
Arm/Group Title RET Mutation Positive Participants
Hide Arm/Group Description

Rearranged during transfection) (RET)

Ponatinib: Ponatinib tablets will be administered orally, continually, once daily at a dose of 30 mg. A cycle of ponatinib is defined as 28 consecutive days starting with the first day of the treatment cycle. Treatment will be administered primarily in an outpatient setting.

All-Cause Mortality
RET Mutation Positive Participants
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
RET Mutation Positive Participants
Affected / at Risk (%) # Events
Total   2/3 (66.67%)    
Gastrointestinal disorders   
Gastric hemorrhage  1  1/3 (33.33%)  1
General disorders   
Death NOS  1  1/3 (33.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
RET Mutation Positive Participants
Affected / at Risk (%) # Events
Total   3/3 (100.00%)    
Blood and lymphatic system disorders   
Anemia  1  2/3 (66.67%)  2
Cardiac disorders   
Sinus tachycardia  1  1/3 (33.33%)  1
Gastrointestinal disorders   
Constipation  1  2/3 (66.67%)  2
Diarrhea  1  1/3 (33.33%)  1
Nausea  1  1/3 (33.33%)  1
Vomiting  1  1/3 (33.33%)  1
General disorders   
Chills  1  1/3 (33.33%)  2
Fatigue  1  2/3 (66.67%)  3
Fever  1  1/3 (33.33%)  2
Localized edema  1  1/3 (33.33%)  1
Pain  1  2/3 (66.67%)  4
Investigations   
Alanine aminotransferase increased  1  1/3 (33.33%)  1
Alkaline phosphatase increased  1  2/3 (66.67%)  3
Aspartate aminotransferase increased  1  1/3 (33.33%)  1
Blood bilirubin increased  1  1/3 (33.33%)  1
Lipase increased  1  3/3 (100.00%)  3
Lymphocyte count decreased  1  2/3 (66.67%)  3
Platelet count decreased  1  1/3 (33.33%)  1
Serum amylase increased  1  1/3 (33.33%)  1
Weight loss  1  1/3 (33.33%)  1
White blood cell decreased  1  1/3 (33.33%)  2
Metabolism and nutrition disorders   
Anorexia  1  1/3 (33.33%)  1
Hypercalcemia  1  1/3 (33.33%)  1
Hypermagnesemia  1  1/3 (33.33%)  1
Hypoalbuminemia  1  3/3 (100.00%)  5
Hyponatremia  1  1/3 (33.33%)  1
Hypophosphatemia  1  1/3 (33.33%)  1
Musculoskeletal and connective tissue disorders   
Back pain  1  1/3 (33.33%)  2
Generalized muscle weakness  1  1/3 (33.33%)  2
Myalgia  1  1/3 (33.33%)  1
Nervous system disorders   
Paresthesia  1  1/3 (33.33%)  1
Psychiatric disorders   
Insomnia  1  1/3 (33.33%)  1
Renal and urinary disorders   
Urinary frequency  1  1/3 (33.33%)  1
Urinary incontinence  1  1/3 (33.33%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  2/3 (66.67%)  3
Skin and subcutaneous tissue disorders   
Pruritus  1  1/3 (33.33%)  1
Rash maculo-papular  1  1/3 (33.33%)  1
Vascular disorders   
Hypertension  1  2/3 (66.67%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
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
Layout table for Results Point of Contact information
Name/Title: Dr. James Gulley
Organization: National Cancer Institute
Phone: 301-496-4916
EMail: gulleyj@mail.nih.gov
Layout table for additonal information
Responsible Party: James Gulley, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT01838642     History of Changes
Other Study ID Numbers: 130108
13-C-0108
First Submitted: April 20, 2013
First Posted: April 24, 2013
Results First Submitted: February 18, 2016
Results First Posted: March 17, 2016
Last Update Posted: February 15, 2017