Malignant Hepatobiliary NeoplasmPhase 2NCT02265341
Ponatinib Hydrochloride in Treating Patients With Advanced Biliary Cancer With FGFR2 Fusions
A Phase 2 study testing Laboratory Biomarker Analysis, Ponatinib Hydrochloride and Quality-of-Life Assessment in people with Malignant Hepatobiliary Neoplasm, run by Mayo Clinic at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Hepatobiliary Neoplasm
- What is being tested?
- Laboratory Biomarker Analysis, Ponatinib Hydrochloride and Quality-of-Life Assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to 14 Jun 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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
Show all 29Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study of Ponatinib in Biliary Cancer Patients With FGFR2 Fusions
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:
- 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:
- 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:
- 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.
- Conditions
- Malignant Hepatobiliary Neoplasm
- Being tested
- Laboratory Biomarker Analysis, Ponatinib Hydrochloride, Quality-of-Life Assessment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
Ponatinib HydrochlorideDrug
Also called AP24534 HCl
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ponatinib hydrochloride) | Experimental | Patients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Other: Laboratory Biomarker Analysis; Drug: Ponatinib Hydrochloride; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 10 months of treatment
Secondary outcomes (4)
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.
Measured: Up to 10 months of treatment
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.
Measured: Up to 10 months of treatment
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.
Measured: Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.
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.
Measured: Time from registration to death due to any cause, assessed up to a maximum of 3.3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2014 (estimated)
- Study startDec 2014
- Primary completion1 May 2018
- Study completion14 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant Hepatobiliary NeoplasmStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mitesh Borad, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02265341
- Sponsor's protocol ID
- MC1345
- Other IDs
- NCI-2014-02075, MC1345, P30CA015083
- Status last verified
- Apr 2019
- First submitted
- 9 Oct 2014
- Last updated
- 25 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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 at a glance
From the registry record, last updated by the sponsor on 25 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Ponatinib in Biliary Cancer Patients With FGFR2 Fusions
- ClinicalTrials.gov ID
- NCT02265341
- Acronym / sponsor ID
- MC1345
- Conditions
- Malignant Hepatobiliary Neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2014 (actual)
- Primary completion
- 1 May 2018 (actual)
- Study completion
- 14 Jun 2019 (actual)
- First posted
- 15 Oct 2014 (estimated)
- Results
- Posted 6 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ponatinib hydrochloride) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Ponatinib Hydrochloride, Other: Quality-of-Life AssessmentPatients receive ponatinib hydrochloride PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (29 listed)
- Any of the following:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (ponatinib hydrochloride) |
| Ponatinib HydrochlorideAlso: AP24534 HClGiven PO | Drug | Treatment (ponatinib hydrochloride) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Treatment (ponatinib hydrochloride) |
Primary outcome
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.
4 secondary outcomes
CA 19-9 Response
Time frame: Up to 10 months of treatment
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
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.
Survival Time
Time frame: Time from registration to death due to any cause, assessed up to a maximum of 3.3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25763789Borad 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.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mitesh Borad principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Laboratory Biomarker Analysis, Ponatinib Hydrochloride and Quality-of-Life Assessment in people with Malignant Hepatobiliary Neoplasm, run by Mayo Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02265341, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2020.