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CompletedNCT02265341Updated Nov 25, 2020Results posted

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

A Phase 2 interventional study of Laboratory Biomarker Analysis and Ponatinib Hydrochloride in Malignant Hepatobiliary Neoplasm, sponsored by Mayo Clinic. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-11-25.

Sponsored by Mayo Clinic · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
12
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This pilot phase II trial studies how well ponatinib hydrochloride works in treating patients with biliary cancer that has spread to other places in the body and that have alterations (fusions) in a gene known as fibroblast growth factor receptor 2 (FGFR2). Ponatinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

OUTLINE:

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.

02

Conditions studied

  • Malignant Hepatobiliary Neoplasm
03

In context

Lead sponsor

Mayo Clinic is the lead sponsor of 3,218 studies on the registry; 670 are open to participants now.

Of its 445 completed or terminated interventional studies of FDA-regulated products, 313 (70%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Histological/cytological confirmation of biliary cancer
  • Confirmation of advanced biliary cancer that is refractory or intolerant to gemcitabine or fluoropyrimidine based therapy with FGFR2 fusion [using next-gen sequencing assays (such as Foundation One) or fluorescent in situ hybridization (FISH) break-apart assays] or FGFR pathway mutation/amplification [using next-gen sequencing assays (such as Foundation One)]; assays must be performed in a Clinical Laboratory Improvement Amendments [CLIA] certified laboratory and done as a CLIA validated test or research use only [RUO] in a CLIA laboratory
  • Measurable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Absolute neutrophil count (ANC) >= 1500/mm\^3
  • Platelet count >= 100,000/mm\^3
  • Hemoglobin >= 9.0 g/dL
  • Total bilirubin =\< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome
  • Aspartate transaminase (AST) and alanine aminotransferase (ALT) \< 3 x ULN
  • Creatinine =\< 1.5 x ULN
  • Serum lipase and amylase =\< 2.5 x ULN; NOTE: if subject has tumor involvement in the liver =\< 3 x ULN
  • Negative pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
  • Recovered from prior radiotherapy and/or systemic therapy related toxicities to grade =\< 1
  • Provide informed written consent
  • Life expectancy >= 3 months
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study); Note: during the Active Monitoring Phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Female and male patients who are fertile agree to use an effective form of contraception with their sexual partners from registration through 4 months after the end of treatment
  • Ability to complete questionnaire(s) by themselves or with assistance

Exclusion criteria

Exclusion Criteria:

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients with a known history of HIV infection are not eligible for this trial
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Prior systemic chemotherapy, radiation therapy or major surgery =\< 30 days prior to registration
  • Concurrent use of any other approved or investigational anticancer agents, including hormonal agents
  • Prior nitrosourea or mitomycin C =\< 6 weeks prior to registration
  • Patients with gastrointestinal comorbidities that would affect intake or absorption of ponatinib
  • Untreated or progressive brain metastases
  • Prior treatment with or allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib
  • Clinically uncontrolled hypertension (diastolic blood pressure > 90 mm mercury [Hg]; systolic > 140 mm Hg); Note: patients with hypertension should be undergoing treatment at study entry for blood pressure control
  • Previous or concurrent malignancy except adequately treated basal or squamous cell skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively and without evidence of recurrence for at least 5 years
  • History of significant bleeding disorder unrelated to cancer
  • History of acute pancreatitis within 1 year prior to registration, chronic pancreatitis, alcohol abuse or uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)

  • Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:

    • Any history of myocardial infarction, stroke, or revascularization
    • Unstable angina or transient ischemic attack within 6 months prior to registration
    • Congestive heart failure within 6 months prior to registration, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to registration
    • History of clinically significant (as determined by the treating physician) atrial arrhythmia
    • Any history of ventricular arrhythmia
    • Active venous thromboembolism including deep venous thrombosis or pulmonary embolism that is not amenable to treatment with anticoagulants
    • Patients with congenital prolonged QT syndromes and abnormal baseline prolonged corrected QT (QTc) (> 450 ms in men and > 470 ms in women)
    • Patients with an ejection fraction =\< 50% as assessed by a baseline echocardiogram
  • Taking medications that are known to be associated with torsades de pointes
  • Taking any medications or herbal supplements that are known to be strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) =\< 14 days prior to registration
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
12 participants (actual)

Study arms

  • 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: Quality-of-Life Assessment

Interventions

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • DrugPonatinib Hydrochloride

    Given PO

    Also known as: AP24534 HCl

  • OtherQuality-of-Life Assessment

    Ancillary studies

    Also known as: Quality of Life Assessment

06

What researchers measure

Primary outcomes

  1. Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)

    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

Secondary outcomes

  1. CA 19-9 Response

    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

  2. Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)

    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

  3. Progression-free Survival

    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.

  4. Survival Time

    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

Other outcomes

  1. 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

    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

  2. Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations

    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

  3. Rate of FGFR Fusions

    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

07

Results

Posted Aug 6, 2019

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Ponatinib Hydrochloride)
Started12
Completed12
Not completed0

Outcome measures

PrimaryClinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)

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
Reported as:
Number · percentage of patients
Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)
percentage of patientsTreatment (Ponatinib Hydrochloride)
Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)45.5 (16.8 to 76.6)
SecondaryCA 19-9 Response

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
Reported as:
Number · percentage of patients
CA 19-9 Response
percentage of patientsTreatment (Ponatinib Hydrochloride)
CA 19-9 Response0
SecondaryOverall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)

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
Reported as:
Number · percentage of patients
Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)
percentage of patientsTreatment (Ponatinib Hydrochloride)
Overall Toxicity Rate, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (v4)41.7
SecondaryProgression-free Survival

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.
Reported as:
Median · months
Progression-free Survival
monthsTreatment (Ponatinib Hydrochloride)
Progression-free Survival2.4 (1.9 to 9.2)
SecondarySurvival Time

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
Reported as:
Median · months
Survival Time
monthsTreatment (Ponatinib Hydrochloride)
Survival Time15.7 (6.1 to NA)
Other pre-specifiedChanges 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

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

Results for this outcome have not been posted.

Other pre-specifiedRate of Circulating-free Tumor Deoxyribonucleic Acid Mutations

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

Results for this outcome have not been posted.

Other pre-specifiedRate of FGFR Fusions

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

Results for this outcome have not been posted.

Adverse events

Collected over Up to a maximum of 10 months on treatment.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Ponatinib Hydrochloride)9/12 (75%)5/12 (41.7%)11/12 (91.7%)
Most frequent serious events
Most frequent serious events
EventTreatment (Ponatinib Hydrochloride)
PancreatitisGastrointestinal disorders1/12
FatigueGeneral disorders1/12
SepsisInfections and infestations1/12
CoughRespiratory, thoracic and mediastinal disorders1/12
Pleural effusionRespiratory, thoracic and mediastinal disorders1/12
Most frequent other events
Showing 10 of 28
Most frequent other events
EventTreatment (Ponatinib Hydrochloride)
FatigueGeneral disorders9/12
Abdominal painGastrointestinal disorders7/12
ConstipationGastrointestinal disorders7/12
Rash maculo-papularSkin and subcutaneous tissue disorders7/12
NauseaGastrointestinal disorders6/12
Edema limbsGeneral disorders5/12
Platelet count decreasedInvestigations5/12
Alkaline phosphatase increasedInvestigations4/12
DiarrheaGastrointestinal disorders3/12
HypertensionVascular disorders3/12

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment (Ponatinib Hydrochloride)
Median48.5 (40.0 to 66.0)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Ponatinib Hydrochloride)
Female9
Male3
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Ponatinib Hydrochloride)
American Indian or Alaska Native1
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American1
White10
More than one race0
Unknown or Not Reported0
ECOG Performance Status
ECOG Performance Status(Participants)Treatment (Ponatinib Hydrochloride)
03
17
22
08

Study locations

1 site
  • Mayo Clinic in Arizona
    Scottsdale, Arizona 85259, United States
09

References and documents

Publications

  • Borad MJ, Gores GJ, Roberts LR. Fibroblast growth factor receptor 2 fusions as a target for treating cholangiocarcinoma. Curr Opin Gastroenterol. 2015 May;31(3):264-8. doi: 10.1097/MOG.0000000000000171. PubMed 25763789 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 13, 2016

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 25, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02265341
Lead sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Oct 15, 2014
Start date
Dec 2014
Primary completion
May 1, 2018
Completion
Jun 14, 2019
Results posted
Aug 6, 2019
Last update
Nov 25, 2020

Study contacts

Mitesh Borad
principal investigator · Mayo Clinic

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Apr 2019. You cannot join it, but the record below documents what was studied.

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