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

NCT02265341 | Completed Phase 2 Results DMC

• 3 other identifiers: MC1345NCI-2014-02075P30CA015083
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malignant Hepatobiliary Neoplasm

Outcome Measures

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.

  Up to 10 months of treatment

Secondary Outcomes (4)

• CA 19-9 Response

  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)

  Up to 10 months of treatment

• Progression-free Survival

  Time from registration to the earliest date of documentation of disease progression, assessed up to maximum 3.3 years from registration.

• Survival Time

  Time from registration to death due to any cause, assessed up to a maximum of 3.3 years

Other Outcomes (3)

• 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

  Up to a maximum follow-up of 3.3 years

• Rate of Circulating-free Tumor Deoxyribonucleic Acid Mutations

  Up to a maximum follow-up of 3.3 years

• Rate of FGFR Fusions

  Up to a maximum follow-up of 3.3 years

Study Arms (1)

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.

Other: Laboratory Biomarker Analysis; Drug: Ponatinib Hydrochloride; Other: Quality-of-Life Assessment

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ponatinib hydrochloride)

Ponatinib Hydrochloride DRUG

Given PO

Also known as: AP24534 HCl

Treatment (ponatinib hydrochloride)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (ponatinib hydrochloride)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Related Publications (1)

• 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.

  PMID: 25763789 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Interventions

ponatinib

Results Point of Contact

• Title: Mitesh J. Borad, MD
• Organization: Mayo Clinic

Borad.Mitesh@mayo.edu

480/301-8335

Study Officials

• Mitesh Borad

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: October 15, 2014
• Study Start: December 1, 2014
• Primary Completion: May 1, 2018
• Study Completion: June 14, 2019
• Last Updated: November 25, 2020
• Results First Posted: August 6, 2019

Record last verified: 2019-04

Locations

US (1)