Efficacy, Safety and Pharmacokinetics Study of Antroquinonol to Treat NSCLC
Condition: Non-small Cell Lung Cancer Stage IV
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Antroquinonol
Intervention description: patients will receive one 12 week cycle of antroquinonol 200 mg t.i.d. or until disease progression, unacceptable toxicity, non compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NSCLC

Summary:

      This is a single arm, open label, Phase II study in KRAS-positive and KRAS-negative patients
      with stage IV (including pleural effusion) non squamous NSCLC who have failed two lines of
      anti-cancer therapy. A maximum of 60 evaluable patients with NSCLC will receive
      antroquinonol, of which 30 patients will be KRAS-positive and 30 patients KRAS-negative. An
      evaluable patient will have received at least one dose of antroquinonol and have a valid
      baseline tumor assessment. Enrollment will continue until the target number of evaluable
      patients has been enrolled.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Cytologically or histologically confirmed non squamous NSCLC Stage IV (including
             pleural effusion).

          -  Radiologically confirmed disease progression following two previous lines of
             anti-cancer therapy, one of which should be a platinum based regimen, OR the patient
             has refused treatment with approved treatment modalities

          -  At least one radiologically measurable target lesion per RECIST version 1.1

          -  Fresh or archival biopsy tissue available to determine tumor mutation status

          -  Written informed consent that is consistent with International Conference on
             Harmonisation Tripartite Guideline on Good Clinical Practice guidelines

          -  Patient or legally acceptable representative has granted written informed consent
             before any study specific procedures (including special Screening tests) are performed

          -  Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2

          -  Hemoglobin ≥ 9.0 g/dL; platelets ≥ 100 x 109/L; absolute neutrophil count ≥ 1.5 x
             109/L without the use of hematopoietic growth factors

          -  Bilirubin and creatinine less than 2 × upper limit of normal (ULN) for the institution

          -  Albumin ≥ 2.5 mg/dL

          -  Aspartate aminotransferase and alanine aminotransferase less than 5 × ULN for the
             institution

          -  Prothrombin time less than 1.5 × ULN for the institution

          -  Potassium, magnesium and phosphorus within the normal range for the institution
             (supplementation is permissible)

          -  Recovery to Grade 1 or baseline of any toxicities due to prior treatments, excluding
             alopecia

        Exclusion Criteria:

          -  Chemo-, hormone- or immunotherapy, within 4 weeks or within less than four half lives
             of the date of first administration of study drug and/or persistence of toxicities of
             prior anti-cancer therapies which are deemed to be clinically relevant

          -  Radiotherapy within the past 2 weeks prior to date of first administration of study
             drug

          -  Previous treatment with an histone deacetylase inhibitor or an epidermal growth factor
             receptor inhibitor within at least 4 weeks of the date of first administration of
             study drug

          -  Treatment with any drug(s) known to be an inhibitor or inducer of cytochrome P450
             (CYP)2C19, CYP3A4, CYP2C8, and CYP2E1, within 14 days of the date of first
             administration of study drug

          -  Brain metastases, which are symptomatic; patients with treated, brain metastases are
             eligible with stable brain disease for at least 4 weeks without the requirement for
             steroids or anti epileptic therapy

          -  Inability to swallow oral medications or a recent acute gastrointestinal disorder with
             diarrhea e.g., Cohn's disease, malabsorption, or Common Terminology Criteria for
             Adverse Event (CTCAE) Grade > 2 diarrhea of any etiology at baseline

          -  Other malignancies diagnosed within the past five years (other than curatively treated
             cervical cancer in situ), non melanoma skin cancer, superficial bladder tumors Ta (non
             invasive tumor) and TIS (carcinoma in situ)

          -  Patients with any serious active infection (i.e., requiring an intravenous antibiotic,
             antifungal, or antiviral agent)

          -  Patients with known human immunodeficiency virus, active hepatitis B or active
             hepatitis C

          -  Patients who have any other life threatening illness or organ system dysfunction,
             which in the opinion of the investigator, would either compromise patient safety or
             interfere with the evaluation of the safety of the study drug

          -  Known or suspected substance abuse or alcohol abuse

          -  Pregnancy or breast feeding

          -  History of clinically significant or uncontrolled cardiac disease, including
             congestive heart failure, angina, myocardial infarction, arrhythmia, including New
             York Heart Association functional classification of three