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Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions

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: NCT02265341
Recruitment Status : Completed
First Posted : October 15, 2014
Results First Posted : August 6, 2019
Last Update Posted : August 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Malignant Hepatobiliary Neoplasm
Interventions Other: Laboratory Biomarker Analysis
Drug: Ponatinib Hydrochloride
Other: Quality-of-Life Assessment
Enrollment 12
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Period Title: Overall Study
Started 12
Completed 12
Not Completed 0
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Baseline Participants 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 12 participants
48.5
(40.0 to 66.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
Female
9
  75.0%
Male
3
  25.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
American Indian or Alaska Native
1
   8.3%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   8.3%
White
10
  83.3%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants
0
3
  25.0%
1
7
  58.3%
2
2
  16.7%
[1]
Measure Description: Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.
1.Primary Outcome
Title Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)
Hide Description A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of clinical benefit rate will be estimated by the number of patients with clinical benefit (confirmed CR, confirmed PR, or SD for 4 or more cycles) divided by the total number of evaluable patients. Complete Response (CR): All of the following must be true:a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD (see Section 11.41). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for PD taking as reference the MSD. Please refer to RECIST v1.1 response criteria for more details.
Time Frame Up to 10 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who received treatment for at least 8 weeks are evaluable for this outcome (i.e. one patient refused further treatment and was therefore unevaluable for response at 8 weeks)
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description:
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of patients
45.5
(16.8 to 76.6)
2.Secondary Outcome
Title CA 19-9 Response
Hide Description This test measures the amount of a protein called CA 19-9 (cancer antigen 19-9) in the blood. CA 19-9 is a type of tumor marker. Tumor markers are substances made by cancer cells or by normal cells in response to cancer in the body.CA 19-9 was collected at baseline and on day one of each cycle. A CA 19-9 response is defined to be a >= 50% reduction from baseline. The CA 19-9 response rate (percentage) will be estimated by the number of CA 19-9 responses divided by the total number of evaluable patients.
Time Frame Up to 10 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Only patients who had baseline and subsequent CA 19-9 levels measured in the study are evaluable for this analysis.
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description:
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 3
Measure Type: Number
Unit of Measure: percentage of patients
0
3.Secondary Outcome
Title Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
Hide Description The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Time Frame Up to 10 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description:
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 12
Measure Type: Number
Unit of Measure: percentage of patients
41.7
4.Secondary Outcome
Title Progression-free Survival
Hide Description Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description:
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: months
2.4
(1.9 to 9.2)
5.Secondary Outcome
Title Survival Time
Hide Description Overall survival time is defined as the time from registration to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.
Time Frame Time from registration to death due to any cause, assessed up to a maximum of 3.3 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description:
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Number of Participants Analyzed 12
Median (95% Confidence Interval)
Unit of Measure: months
15.7 [1] 
(6.1 to NA)
[1]
The 95% Confidence interval upper limit was not able to be estimated due to an insufficient number of participants with events.
6.Other Pre-specified Outcome
Title Changes in Patient-reported Outcomes (Quality of Life and Symptoms), Assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30, EORTC QLQ-BIL21, Skindex-16, and Bowel Function Questionnaire
Hide Description The Uniscale assessment of overall quality of life will be used. The Was It Worth It questionnaire will determine patient's satisfaction with the study. Scale score trajectories over time will be examined using stream plots and mean plots with standard deviation error bars overall. Changes from baseline at each cycle will be statistically tested using paired t-tests, and standardized response means will be interpreted using Cohen's (1988) cut-offs. Correlation between outcomes will employ Pearson and/or Spearman correlations at individual time points.
Time Frame Up to a maximum follow-up of 3.3 years
Outcome Measure Data Not Reported
7.Other Pre-specified Outcome
Title Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations
Hide Description Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.
Time Frame Up to a maximum follow-up of 3.3 years
Outcome Measure Data Not Reported
8.Other Pre-specified Outcome
Title Rate of FGFR Fusions
Hide Description Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.
Time Frame Up to a maximum follow-up of 3.3 years
Outcome Measure Data Not Reported
Time Frame Up to a maximum of 10 months on treatment.
Adverse Event Reporting Description Each CTCAE term is a representation of a specific event used for medical documentation & analysis & is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for all patients. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, & appear in the SAE table.
 
Arm/Group Title Treatment (Ponatinib Hydrochloride)
Hide Arm/Group Description Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All-Cause Mortality
Treatment (Ponatinib Hydrochloride)
Affected / at Risk (%)
Total   9/12 (75.00%)    
Hide Serious Adverse Events
Treatment (Ponatinib Hydrochloride)
Affected / at Risk (%) # Events
Total   5/12 (41.67%)    
Gastrointestinal disorders   
Pancreatitis  1  1/12 (8.33%)  1
General disorders   
Fatigue  1  1/12 (8.33%)  1
Infections and infestations   
Sepsis  1  1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/12 (8.33%)  1
Pleural effusion  1  1/12 (8.33%)  1
1
Term from vocabulary, MedDRA 12
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Treatment (Ponatinib Hydrochloride)
Affected / at Risk (%) # Events
Total   11/12 (91.67%)    
Blood and lymphatic system disorders   
Anemia  1  1/12 (8.33%)  1
Gastrointestinal disorders   
Abdominal pain  1  7/12 (58.33%)  17
Constipation  1  7/12 (58.33%)  21
Diarrhea  1  3/12 (25.00%)  7
Nausea  1  6/12 (50.00%)  18
Vomiting  1  2/12 (16.67%)  5
General disorders   
Edema limbs  1  5/12 (41.67%)  11
Fatigue  1  9/12 (75.00%)  41
Fever  1  1/12 (8.33%)  1
Investigations   
Alanine aminotransferase increased  1  2/12 (16.67%)  3
Alkaline phosphatase increased  1  4/12 (33.33%)  8
Blood bilirubin increased  1  1/12 (8.33%)  2
CD4 lymphocytes decreased  1  1/12 (8.33%)  1
Lymphocyte count decreased  1  1/12 (8.33%)  1
Neutrophil count decreased  1  1/12 (8.33%)  1
Platelet count decreased  1  5/12 (41.67%)  22
White blood cell decreased  1  1/12 (8.33%)  1
Metabolism and nutrition disorders   
Anorexia  1  2/12 (16.67%)  2
Hyperglycemia  1  1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders   
Arthralgia  1  1/12 (8.33%)  1
Back pain  1  1/12 (8.33%)  1
Nervous system disorders   
Headache  1  1/12 (8.33%)  2
Respiratory, thoracic and mediastinal disorders   
Cough  1  2/12 (16.67%)  3
Hoarseness  1  1/12 (8.33%)  1
Pneumonitis  1  1/12 (8.33%)  1
Skin and subcutaneous tissue disorders   
Dry skin  1  1/12 (8.33%)  1
Rash maculo-papular  1  7/12 (58.33%)  21
Vascular disorders   
Hypertension  1  3/12 (25.00%)  6
1
Term from vocabulary, MedDRA 12
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mitesh J. Borad, MD
Organization: Mayo Clinic
Phone: 480/301-8335
EMail: Borad.Mitesh@mayo.edu
Layout table for additonal information
Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT02265341    
Other Study ID Numbers: MC1345
NCI-2014-02075 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1345 ( Other Identifier: Mayo Clinic in Arizona )
P30CA015083 ( U.S. NIH Grant/Contract )
First Submitted: October 9, 2014
First Posted: October 15, 2014
Results First Submitted: June 3, 2019
Results First Posted: August 6, 2019
Last Update Posted: August 6, 2019