Pilot Study of Ponatinib in Biliary Cancer Patients With FGFR2 Fusions
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Laboratory Biomarker Analysis (Other)
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.
干预措施: Ponatinib Hydrochloride (Drug)
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.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Clinical Benefit Rate (Percentage), Which Includes Confirmed Tumor Response (Complete Response [CR] or Partial Response [PR]) or Stable Disease (SD)
时间窗: 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.
次要结局
- Survival Time(Time from registration to death due to any cause, assessed up to a maximum of 3.3 years)
- 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.)