Clinical Trials /

Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers

NCT01935336

Description:

This phase II trial studies how well ponatinib hydrochloride works in treating patients with stage III-IV lung cancer. Ponatinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Lung Adenocarcinoma
  • Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Ponatinib</span> in Patients With <span class="go-doc-concept go-doc-disease">Lung Cancer</span> Preselected Using Different Candidate Predictive Biomarkers

Title

  • Brief Title: Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
  • Official Title: A Phase II Study of Ponatinib in Cohorts of Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers
  • Clinical Trial IDs

    NCT ID: NCT01935336

    ORG ID: 13-2002.cc

    NCI ID: NCI-2013-01644

    Trial Conditions

    Adenocarcinoma of the Lung

    Extensive Stage Small Cell Lung Cancer

    Limited Stage Small Cell Lung Cancer

    Recurrent Non-small Cell Lung Cancer

    Recurrent Small Cell Lung Cancer

    Stage IIIA Non-small Cell Lung Cancer

    Stage IIIB Non-small Cell Lung Cancer

    Stage IV Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ponatinib Iclusig, AP24534, Multitargeted tyrosine kinase inhibitor AP24534 Ponatinib

    Trial Purpose

    This phase II trial studies how well ponatinib hydrochloride works in treating patients with
    stage III-IV lung cancer. Ponatinib hydrochloride may stop the growth of tumor cells by
    blocking some of the enzymes needed for cell growth.

    Detailed Description

    This study will look at the safety and effectiveness of the investigational drug ponatinib
    in lung cancer. The investigators hope that ponatinib will work against tumors that have
    certain biomarkers. Therefore, the study will pre-screen patients for these certain
    biomarkers before enrolling them into the main treatment study. Different doses of ponatinib
    may be tested in this study.

    Trial Arms

    Name Type Description Interventions
    Ponatinib Experimental Patients receive ponatinib hydrochloride taken by mouth once or twice a day. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Ponatinib

    Eligibility Criteria

    Inclusion Criteria:

    - PART A: Patients must have histologically or cytologically confirmed locally advanced
    (after failure of local therapy) or metastatic lung cancer (any histology, except
    carcinoid) stage IIIa, IIIb or IV

    - PART A: Existing formalin fixed paraffin embedded biopsy of the lung cancer with
    potentially sufficient material for analysis

    - PART A: Non-small cell lung cancer (NSCLC) with adenocarcinoma histology must have
    been previously tested for both epidermal growth factor receptor (EGFR) mutations and
    anaplastic lymphoma kinase (ALK) rearrangements

    - PART A: Able (physically and financially) to travel to University of Colorado for
    clinical trial treatment

    - PART B: Patients must have histologically or cytologically confirmed locally advanced
    (after failure of local therapy) or metastatic lung cancer (any histology, except
    carcinoid) stage IIIa, IIIb or IV

    - PART B: Patients must be proven to meet marker criteria (FGFR1 silver in situ
    hybridization (SISH) + in situ hybridization (ISH) +, FGFR1 SISH+ ISH negative [-ve],
    FGFR1 SISH-ve ISH+, FGFR1 SISH-ve ISH-ve [FGFR1 double negative cohort] or ret
    proto-oncogene [RET] FISH+) prior to enrollment into Part B (treatment);
    adenocarcinoma patients must be known to not possess either an EGFR mutation or an
    ALK rearrangement in their tumor (if positive for one, testing for both is not
    required)

    - PART B: Patients must have measurable disease as per Response Evaluation Criteria in
    Solid Tumors (RECIST) version 1.1

    - PART B: Patients may have received any number of lines of prior therapy

    - PART B: Life expectancy of >= 3 months

    - PART B: Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky
    >= 60%)

    - PART B: Leukocytes >= 3,000/mcL

    - PART B: Absolute neutrophil count >= 1,500/mcL

    - PART B: Hemoglobin >= 9 g/dL

    - PART B: Platelets >= 100,000/mcL

    - PART B: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN), unless
    due to Gilbert's syndrome

    - PART B: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
    [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
    =< 2.5 X ULN

    - PART B: Creatinine =< 1.5 X ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for
    patients with creatinine levels above institutional normal

    - PART B: Serum lipase =< 1.5 X ULN

    - PART B: Serum amylase =< 1.5 X ULN

    - PART B: Previous treatment related side-effects/adverse events must have resolved to
    at least grade 1 or, at the discretion of the investigator, select stable grade 2
    toxicities (e.g. alopecia or fatigue) may be permissible if unchanging in grade for
    at least 3 months following discussion with the principal investigator (PI)

    - PART B: Patients with central nervous system (CNS) metastases are eligible for
    enrollment if they have no overt evidence of neurological deficits, and are not
    requiring anti-epileptics or steroids to control their neurological symptoms;
    patients with known CNS metastases must have relevant CNS imaging performed
    approximately coincident with body imaging during response assessments

    - PART B: The effects of ponatinib on the developing human fetus are unknown; for this
    reason women of child-bearing potential must have a negative urine or blood pregnancy
    test at screening for Part B; women of child-bearing potential and men must also have
    documented agreement to use adequate contraception (hormonal or barrier method of
    birth control; abstinence) from the time of screening until 30 days after the end of
    study treatment; should a woman become pregnant or suspect she is pregnant while she
    or her partner are participating in this study, they should inform the treating
    physician immediately

    - PART B: Ability to understand and the willingness to sign a written informed consent
    document

    Exclusion Criteria:

    - PART A: Known EGFR mutation and/or ALK rearrangement in NSCLC with adenocarcinoma
    histology

    - PART B: No previous treatment with a standard or investigational anti-cancer agent
    within predicted 5 half-lives of the agent; or 28 days whichever is the shorter; if
    the plasma half-life is not known or the previous therapy was a monoclonal antibody
    then a 28 day washout period will be considered as the default requirement

    - PART B: No previous or current exposure to other FGFR inhibitors in the FGFR-selected
    cohorts, or RET inhibitors in the RET selected cohorts

    - PART B: Prior radiotherapy to proposed target lesions is not permitted unless
    completed more than 4 weeks prior to treatment within the study and that there has
    been documented progression at these sites; radiotherapy to non-target lesions is
    permitted within 2 weeks of study entry provided all acute effects of the
    radiotherapy have resolved to =< grade 1

    - PART B: History of allergic or severe reactions attributed to compounds of similar
    chemical or biologic composition to ponatinib

    - PART B: Ponatinib is a substrate for cytochrome P450, family 3, subfamily A,
    polypeptide 4/5 (CYP3A4/5), concurrent use with potent CYP3A4/5 inhibitors or
    inducers should be undertaken with caution

    - PART B: History of clinically significant bleeding disorder

    - PART B: History of acute pancreatitis within 1 year of study or history of chronic
    pancreatitis

    - PART B: Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)

    - PART B: Uncontrolled intercurrent illness including, but not limited to:

    - Ongoing or active infection requiring intravenous antibiotics

    - Psychiatric illness/social situations that would limit compliance with study
    requirements

    - Congestive heart failure, unstable angina pectoris, or myocardial infarction
    within the 3 months prior to enrollment in part B of the study

    - History of clinically significant (as determined by the treating medical doctor
    [MD]) cardiac arrhythmia (atrial or ventricular)

    - PART B: Patients who have had major surgery within 28 days prior to entering the
    study or those who have not recovered from adverse events > grade 1 relating to the
    surgery

    - PART B: Pregnant or breastfeeding women

    - PART B: Patients with inability to take oral medications, or, in the investigator's
    opinion, gastrointestinal conditions or abnormalities likely to influence the
    absorption of oral medications

    - PART B: Concomitant use of medications known to be associated with
    torsades-de-pointes

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Prevalence of each biomarker (Part A)

    Overlapping frequency of biomarkers (Part A)

    Objective response rate (ORR) per RECIST v1.1 (Part B)

    Secondary Outcome Measures

    Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0

    Trial Keywords

    Lung Cancer

    Malignancy

    Predictive biomarkers