Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions
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|ClinicalTrials.gov Identifier: NCT02265341|
Recruitment Status : Completed
First Posted : October 15, 2014
Results First Posted : August 6, 2019
Last Update Posted : August 6, 2019
|Condition or disease||Intervention/treatment||Phase|
|Malignant Hepatobiliary Neoplasm||Other: Laboratory Biomarker Analysis Drug: Ponatinib Hydrochloride Other: Quality-of-Life Assessment||Phase 2|
I. To assess the clinical benefit rate (confirmed complete or partial response or stable disease for 4 or more cycles) of ponatinib (ponatinib hydrochloride) in fibroblast growth factor receptor (FGFR) aberrant advanced biliary cancers.
I. To estimate progression free survival, overall survival, and cancer antigen 19-9 (CA19-9) response rate of these patients.
II. To estimate the adverse event profile of ponatinib.
I. Establish preliminary correlations between FGFR2 fusions and evidence of any clinical benefit.
II. Assess preliminary evaluation of FGFR2 pathway perturbation with ponatinib. III. To describe patient-reported health-related quality of life and symptoms.
Patients receive ponatinib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 months for at least 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Pilot Study of Ponatinib in Biliary Cancer Patients With FGFR2 Fusions|
|Actual Study Start Date :||December 2014|
|Actual Primary Completion Date :||May 1, 2018|
|Actual Study Completion Date :||June 14, 2019|
Experimental: Treatment (ponatinib hydrochloride)
Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Drug: Ponatinib Hydrochloride
Other Name: AP24534 HCl
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD) [ Time Frame: Up to 10 months of treatment ]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.
- CA 19-9 Response [ Time Frame: Up to 10 months of treatment ]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.
- Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4) [ Time Frame: Up to 10 months of treatment ]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.
- Progression-free Survival [ Time Frame: Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration. ]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.
- Survival Time [ Time Frame: Time from registration to death due to any cause, assessed up to a maximum of 3.3 years ]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.
- 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 [ Time Frame: Up to a maximum follow-up of 3.3 years ]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.
- Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations [ Time Frame: Up to a maximum follow-up of 3.3 years ]Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.
- Rate of FGFR Fusions [ Time Frame: Up to a maximum follow-up of 3.3 years ]Will be described, and association with confirmed tumor response and/or clinical benefit will be investigated using a Fisher's exact test.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02265341
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259|
|Principal Investigator:||Mitesh Borad||Mayo Clinic|