Ponatinib in Advanced NSCLC w/ RET Translocations
Condition: Non Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Ponatinib
Intervention description: 28 day cycle
Intervention MeSH terms: Ponatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: RET gene mutation

Summary:

      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.
    

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

          -  History of arterial thrombotic events (myocardial infarction, stroke or peripheral
             vascular disease).

          -  Uncontrolled hypertension

          -  Taking medications that are known to be associated with Torsades de Pointes

          -  Ongoing active infection

          -  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