Trial Outcomes & Findings for Ponatinib for Advanced Medullary Thyroid Cancer (NCT NCT01838642)

Last Updated: 2017-02-15

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

2-4 months

Results posted on

2017-02-15

Participant Flow

No participants were enrolled in the RET mutation negative group; study closed prematurely.

Participant milestones

Participant milestones
Measure	RET Mutation Positive Participants. 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 Study STARTED	3
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	RET Mutation Positive Participants. 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 Study Died on study	1

Baseline Characteristics

Ponatinib for Advanced Medullary Thyroid Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RET Mutation Positive Participants n=3 Participants 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.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	59.13 years STANDARD_DEVIATION 5.83 • n=5 Participants
Gender Female	2 Participants n=5 Participants
Gender Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 2-4 months

Population: No participants were enrolled in the RET mutation negative group; study closed prematurely.

Outcome measures

Outcome measures
Measure	RET Mutation Positive Participants n=3 Participants 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 Response Rate. Complete Response	0 percentage of participants
Overall Response Rate. Partial Response	0 percentage of participants

SECONDARY outcome

Timeframe: 2-4 months

Population: No participants were enrolled in the RET mutation negative group; study closed prematurely.

Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

Outcome measures

Outcome measures
Measure	RET Mutation Positive Participants n=3 Participants 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.
Progression Free Survival	3.01 months Interval 2.07 to 4.13

SECONDARY outcome

Timeframe: 17 months and 19 days

Population: No participants were enrolled in the RET mutation negative group; study closed prematurely.

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

Outcome measures

Outcome measures
Measure	RET Mutation Positive Participants n=3 Participants 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.
Number of Participants With Adverse Events	3 participants

SECONDARY outcome

Timeframe: Prior to the first dose of ponatinib

Population: 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.

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.

Outcome measures

Outcome measures
Measure	RET Mutation Positive Participants n=3 Participants 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.
Molecular Differences in Advanced Medullary Thyroid Cancer (MTC) RET mutation	3 participants
Molecular Differences in Advanced Medullary Thyroid Cancer (MTC) RAS mutation	0 participants

SECONDARY outcome

Timeframe: Baseline to 4 weeks

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 4 cycles of treatment with ponatinib

Population: One participant died on study during cycle 2. No participants were enrolled in the RET mutation negative group; study closed prematurely.

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.

Outcome measures

Outcome measures
Measure	RET Mutation Positive Participants n=2 Participants 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.
Objective Response to Ponatinib Complete Response (CR)	0 participants
Objective Response to Ponatinib Partial Response (PR)	0 participants
Objective Response to Ponatinib Progressive Disease (PD)	2 participants
Objective Response to Ponatinib Stable Disease (SD)	0 participants

SECONDARY outcome

Timeframe: Baseline to 4 weeks

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 6 months

Population: No participants were enrolled in the RET mutation negative group; study closed prematurely.

Overall survival is defined as the time between the first day of treatment to the day of disease progression.

Outcome measures

Outcome measures
Measure	RET Mutation Positive Participants n=3 Participants 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 Survival	4.7 months Interval 2.1 to 6.0

Adverse Events

RET Mutation Positive Participants

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	RET Mutation Positive Participants n=3 participants at risk 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.
General disorders Death NOS	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Gastrointestinal disorders Gastric hemorrhage	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.

Other adverse events

Other adverse events
Measure	RET Mutation Positive Participants n=3 participants at risk 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.
Investigations Alanine aminotransferase increased	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Alkaline phosphatase increased	66.7% 2/3 • Number of events 3 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Metabolism and nutrition disorders Anorexia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Blood bilirubin increased	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
General disorders Chills	33.3% 1/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Gastrointestinal disorders Constipation	66.7% 2/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Respiratory, thoracic and mediastinal disorders Dyspnea	66.7% 2/3 • Number of events 3 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
General disorders Fatigue	66.7% 2/3 • Number of events 3 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
General disorders Fever	33.3% 1/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	33.3% 1/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Metabolism and nutrition disorders Hypercalcemia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Metabolism and nutrition disorders Hypermagnesemia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Vascular disorders Hypertension	66.7% 2/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 3/3 • Number of events 5 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Metabolism and nutrition disorders Hyponatremia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Metabolism and nutrition disorders Hypophosphatemia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Psychiatric disorders Insomnia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Lipase increased	100.0% 3/3 • Number of events 3 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
General disorders Localized edema	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Lymphocyte count decreased	66.7% 2/3 • Number of events 3 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
General disorders Pain	66.7% 2/3 • Number of events 4 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Nervous system disorders Paresthesia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Platelet count decreased	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Skin and subcutaneous tissue disorders Pruritus	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Skin and subcutaneous tissue disorders Rash maculo-papular	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Serum amylase increased	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Cardiac disorders Sinus tachycardia	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Renal and urinary disorders Urinary frequency	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Renal and urinary disorders Urinary incontinence	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Gastrointestinal disorders Vomiting	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations Weight loss	33.3% 1/3 • Number of events 1 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.
Investigations White blood cell decreased	33.3% 1/3 • Number of events 2 • 17 months and 19 days No participants were enrolled in the RET mutation negative group; study closed prematurely.

Additional Information

Dr. James Gulley

National Cancer Institute

Phone: 301-496-4916

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place