Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Trial record 14 of 32 for:    ponatinib

Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Ohio State University Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Sameek Roychowdhury, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02272998
First received: October 21, 2014
Last updated: May 6, 2016
Last verified: May 2016
  Purpose
This phase II trial studies how well ponatinib hydrochloride works in treating patients with cancer that has spread to other parts of the body (metastatic), has failed previous treatment (refractory), and has one of several alterations, or mutations, in its deoxyribonucleic acid (DNA) sequence. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether a patient's genetic alterations may affect how well ponatinib hydrochloride works.

Condition Intervention Phase
Malignant Neoplasm
Drug: ponatinib hydrochloride
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Ponatinib for Advanced Cancers With Genomic Alterations in Fibroblastic Growth Factor Receptor (FGFR) and Other Genomic Targets (KIT, PDGFRá, RET FLT3, ABL1)

Resource links provided by NLM:


Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Overall response, defined as the number of patients who achieve any response according to disease type in the first 6 courses of treatment [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    The proportion of responses for the purposes of the decision rule will be calculated out of all eligible patients who receive any treatment. Assuming the number of responses is binomially distributed, 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.


Secondary Outcome Measures:
  • Incidence of toxicity, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
    Frequency and severity of adverse events will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns for each of the cohorts as well as across cohorts. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing.

  • Tolerability of the regimen, assessed by the number of patients who required dose modifications and/or dose delays [ Time Frame: Up to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
    Collected and summarized by descriptive statistics. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.

  • Overall survival [ Time Frame: The time from treatment initiation to death, assessed up to 52 weeks ] [ Designated as safety issue: Yes ]
    Kaplan-Meier curves will be used to estimate the survival distribution.

  • Progression free survival [ Time Frame: The time from treatment initiation to progression or death, assessed up to 52 weeks ] [ Designated as safety issue: Yes ]
    Kaplan-Meier curves will be used to estimate the survival distribution.

  • Clinical benefit rate (CBR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Calculated by the number of patients who have achieve a response and/or are progression-free and alive at 6 months divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for CBR will be calculated.


Other Outcome Measures:
  • Correlative gene and protein markers [ Time Frame: Up to 3 years (time of progression) ] [ Designated as safety issue: No ]
    Correlative gene and protein markers will be summarized univariately in a quantitative manner and also summarized by clinical outcome group (e.g. response vs. no response). Graphical analyses will be largely used to assess potential patterns and relationships; e.g. side-by-side boxplots to assess differences in continuous marker levels between those with vs. without the clinical improvement (e.g. response vs. no response). Overall, hypothesis testing will largely be avoided given the sample size limitations.


Estimated Enrollment: 45
Study Start Date: February 2015
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: ponatinib hydrochloride
Given PO
Other Names:
  • AP24534
  • Iclusig
  • multitargeted tyrosine kinase inhibitor AP24534
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the response of ponatinib (ponatinib hydrochloride) in patients with fibroblast growth factor receptor (FGFR) altered cancers.

SECONDARY OBJECTIVES:

I. To assess the safety and tolerability of ponatinib in advanced solid tumors with genomic FGFR alterations.

II. To assess progression free survival (PFS) and overall survival (OS) with ponatinib.

III. To determine candidate genomic and proteomic biomarkers of sensitivity and resistance to ponatinib using unbiased high throughput approaches (exome, transcriptome, reverse phase protein array [RPPA]).

IV. To assess response of ponatinib in advanced cancers with subsets of genomic FGFR alterations (fusions vs. amplifications vs. mutations).

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 for 52 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed diagnosis of refractory metastatic solid tumor or chronic hematological malignancy who are eligible for investigational drug therapy
  • Patients must have tumor suitable for biopsy (as assessed by trained specialists in interventional radiology) and medically fit to undergo a biopsy or surgical procedure OR if patients do not have a tumor suitable for biopsy but have another tissue available for molecular evaluation
  • Patients should have activating genomic alterations in FGFR (mutations, fusions or amplifications [> 6 copies]) or activating genomic alterations in KIT, platelet-derived growth factor receptor alpha [PDGFRα], ret proto-oncogene [RET], ABL proto-oncogene 1, non-receptor tyrosine kinase [ABL1] and fms-related tyrosine kinase 3 [FLT3] by any validated Clinical Laboratory Improvement Amendments [CLIA]-certified molecular testing (fluorescent in situ hybridization [FISH], polymerase chain reaction [PCR] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable; additional types of activating alterations in these genes can be approved by the principal investigator (PI)
  • Patients with advanced cancers should have had at least one prior therapy that is considered standard for that disease type
  • Patients with solid tumors must have measurable disease (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1), defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 80%)
  • Life expectancy of greater than 3 months
  • Patients with multiple malignancies remain eligible
  • Patients with an inherited cancer syndrome or a medical history suggestive of an inherited cancer syndrome remain eligible
  • Patients must have controlled blood pressure with a systolic blood pressure < 140 mmHg and diastolic < 90 mmHg; anti-hypertensive medications are permitted
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and through 4 months after the end of treatment; for females of childbearing potential, a negative pregnancy test must be documented prior to randomization
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 75,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome (< 5 if liver involvement with primary tumor)
  • Serum lipase and amylase =< 1.5 x ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal by echocardiogram (ECHO) or multi gated acquisition (MUGA)
  • Serum creatinine =< 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) >= 50 mL/min OR 24-hour urine creatinine clearance >= 50 mL/min
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients with acute hematological malignancies (e.g. acute myeloid leukemia)
  • Major surgery (e.g. thoracic, abdominal, vascular, neurosurgery) within 28 days prior to initiating therapy
  • History of acute pancreatitis within one year of study or history of chronic pancreatitis
  • History of alcohol abuse
  • Have uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)
  • Patients who are receiving any other investigational therapeutic agents
  • Patients with gastrointestinal stromal tumor (GIST)
  • Patients with history of clinically significant bleeding disorder
  • Patients with chronic myelocytic or myelogenous leukemia (CML)
  • Patients with multiple myeloma and t(4; 14) translocation with aberrant expression of wild type FGFR3 by immunoglobulin (IgH) promoter (conversely, patients with t (4; 14) translocation and FGFR3 mutation remain eligible)
  • Pregnant women are excluded from this study; breastfeeding should be discontinued
  • Patients who are incarcerated are not eligible
  • Patients with any history of arterial thromboembolic disease; any patient with a history of myocardial infarction (MI), stroke, transient ischemic attack (TIA), unstable angina or peripheral vascular disease will not be eligible
  • Patients with history of recurrent venous thromboembolism (deep venous thrombosis or pulmonary embolism) or history of venous thromboembolism within 6 months will not be eligible
  • Patients with history of active hepatitis B or C infection or chronic hepatitis with Child Pugh B or C hepatic dysfunction
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib
  • Patients with history of atrial arrhythmia (requiring any anti-arrhythmic therapy) or patients with any history of ventricular arrhythmia are excluded
  • Clinically significant, uncontrolled intercurrent illness including, but not limited to:

    • Symptomatic or active infection
    • Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control
    • Psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with history of congestive heart failure or LVEF less than lower limit of normal per local institutional standards are excluded
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Patients on medications known to be associated with Torsades de Pointes
  • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients taking medications or herbal supplements that are known to be strong cytochrome P450 3A4 (CYP3A4) inhibitors within at least 14 days before the first dose of ponatinib are excluded
  • Patients with symptomatic or progressive brain metastases are ineligible; subjects with treated brain metastases are eligible if they have no radiographic or other signs of progression in the brain for >= 4 weeks after completion of local therapy
  • Patients who have received prior FGFR targeted therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02272998

Contacts
Contact: The Ohio State University Comprehensive Cancer Center 1-800-293-5066 Jamesline@osumc.edu

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Ajjai Alva, MD    734-936-8906    Ajjai@med.umich.edu   
Principal Investigator: Ajjai Alva         
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Sameek Roychowdhury, MD    614-685-5842    Sameek.Roychowdhury@osumc.edu   
Principal Investigator: Sameek Roychowdhury, MD         
Sponsors and Collaborators
Sameek Roychowdhury
Investigators
Principal Investigator: Sameek Roychowdhury, MD, PhD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: Sameek Roychowdhury, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02272998     History of Changes
Other Study ID Numbers: OSU-14078  NCI-2014-01499 
Study First Received: October 21, 2014
Last Updated: May 6, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Ohio State University Comprehensive Cancer Center:
FGFR, RET, KIT

Additional relevant MeSH terms:
Neoplasms
Ponatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016