Clinical Trials /

Ponatinib in Advanced NSCLC w/ RET Translocations

NCT01813734

Description:

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It has been found that some people with NSCLC have a change (mutation) in a certain gene called the RET gene. This mutated gene may help cancer cells grow. Only participants with a RET mutation will be allowed to participate. In this study, investigators are testing the strategy of using a study drug designed to inhibit or shut off growth signals that results from the mutated RET gene. Ponatinib is an anti-cancer drug that has been used in research studies for other types of cancer. Ponatinib blocks several growth signals in cancer cells, including RET. In this research study, investigators are looking to see whether ponatinib is effective and safe in treating NSCLC harboring RET rearrangements.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Ponatinib</span> in Advanced NSCLC w/ <span class="go-doc-concept go-doc-biomarker">RET</span> <span class="go-doc-concept go-doc-keyword">Translocations</span>

Title

  • Brief Title: Ponatinib in Advanced NSCLC w/ RET Translocations
  • Official Title: A Phase II, Open-Label Study of Ponatinib, A Multi-Targeted Oral Tyrosine Kinase Inhibitor, in Advanced Non-Small Cell Lung Cancer Harboring RET Translocations
  • Clinical Trial IDs

    NCT ID: NCT01813734

    ORG ID: 13-103

    Trial Conditions

    Non Small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Ponatinib Ponatinib Treatment Arm

    Trial Purpose

    This research study is a Phase II clinical trial, which tests the safety and effectiveness
    of an investigational drug to learn whether the drug works in treating a specific cancer.
    "Investigational" means that the drug is being studied.

    It has been found that some people with NSCLC have a change (mutation) in a certain gene
    called the RET gene. This mutated gene may help cancer cells grow. Only participants with a
    RET mutation will be allowed to participate. In this study, investigators are testing the
    strategy of using a study drug designed to inhibit or shut off growth signals that results
    from the mutated RET gene.

    Ponatinib is an anti-cancer drug that has been used in research studies for other types of
    cancer. Ponatinib blocks several growth signals in cancer cells, including RET. In this
    research study, investigators are looking to see whether ponatinib is effective and safe in
    treating NSCLC harboring RET rearrangements.

    Detailed Description

    Participants in this research study will be asked to undergo some screening tests or
    procedures to confirm that eligibility. Many of these tests and procedures are likely to be
    part of regular cancer care and may be done even if it turns out that participants do not
    take part in the research study. These tests and procedures include the following: medical
    history, vital signs, physical exam, performance status, electrocardiogram, echocardiogram,
    routine blood tests, pregnancy test and an assessment of tumor by CT or MRI. If these tests
    show that a participant is eligible to participate in the research study, he/she will begin
    the study treatment. If a patient does not meet the eligibility criteria, he/she will not be
    able to participate in this research study.

    Participants will take the study drug once a day, every day of the cycle. Each treatment
    cycle lasts 28 days (4 weeks). Participants will be given a drug diary to record the drug
    they take each day. The diary will also include special instructions for taking the study
    drug.

    For cycles 1-20, participants will visit the clinic to have tests and procedures done at the
    time points listed here: On Day 1-physical exam, vital signs, performance status,
    electrocardiogram, routine blood tests, pharmacokinetic test, clinical exam and assessment
    of tumor. On day 15 of cycle 1-vital signs, routine blood tests and clinical exam.

    For cycles 11 and on, participants will visit the clinic every 6 weeks. Some of these visits
    will happen on Day 1 of the cycle and some of these visits will happen on Day 15 of the
    cycle. At each visit, the following tests and procedures will be done: physical exam, vital
    signs, performance status, electrocardiogram, routine blood tests, clinical exam, and an
    assessment of your tumor.

    Participants will visit the clinic when their study doctor takes them off study drug
    permanently. They will also visit the clinic 30 days after stop taking the study drug. The
    following tests and procedures will be done: physical exam, vital signs, performance status,
    electrocardiogram, routine blood tests, pregnancy test, clinical exam and a tumor
    assessment.

    Investigators would also like to keep track of participant's medical condition for two years
    after their first study dose. Investigators will contact participants by telephone every 3
    months. If participants still come to the clinic, visits might be used as contact.

    Trial Arms

    Name Type Description Interventions
    Ponatinib Treatment Arm Experimental Ponatinib 45 mg PO daily Ponatinib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed advanced NSCLC

    - Molecular confirmation of a RET translocation

    - At least one measurable lesion as defined by RECIST

    - No restriction on number of prior therapies

    - Estimated life expectancy of at least 12 weeks

    - Able to swallow and retain orally administered medication

    - Must agree to use an effective form of contraception from enrollment through 30 days
    after the end of study treatment

    - Willingness and ability to comply with scheduled visits and study procedures

    Exclusion Criteria:

    - Clinically significant gastrointestinal abnormalities

    - Pregnant or breastfeeding

    - Major surgery within 28 days of initiating therapy

    - History of CNS disease (Note: Participants with brain metastases will be eligible if
    treated appropriately and if they remain clinically stable).

    - Anti-cancer therapy within 3 weeks

    - History of significant bleeding disorder unrelated to cancer

    - History of acute pancreatitis within 1 year of study entry or history of chronic
    pancreatitis

    - History of alcohol abuse

    - Uncontrolled hypertriglyceridemia

    - Significant uncontrolled or active cardiovascular disease

    - Uncontrolled hypertension

    - Taking medications that are known to be associated with Torsades de Pointes

    - Ongoing active infection

    - Known history of HIV

    - Diagnosed with or received anti-cancer therapy for another primary malignancy within
    3 years prior to entry (except for non-melanoma skin cancer or in situ cancers)

    - Any condition or illness tha could compromise patient safety or interfere with the
    evaluation of the drug

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Response Rate

    Secondary Outcome Measures

    Disease Control Rate

    Progression-Free Survival

    1 Year Overall Survival Rate

    Number of participants with adverse events

    Plasma concentrations of ponatinib

    Trial Keywords

    RET gene mutation