Pharmacokinetic Study of Oral IXAZOMIB in Cancer Patients With Liver Dysfunction
Condition: Advanced Solid Tumors; Hematologic Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms; Liver Diseases
Intervention: IXAZOMIB
Intervention MeSH terms: Ixazomib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase 1, 2-part, pharmacokinetic study in patients with advanced solid tumors or
      hematologic malignancies and varying degrees of liver dysfunction (normal function, moderate
      hepatic impairement or severe hepatic impairment) as defined by the National Cancer Institute
      (NCI) Organ Dysfunction Working Group.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years or older

          -  Patients must have a diagnosis of an advanced malignant solid tumor or hematologic
             malignancy for which standard, curative, or life-prolonging treatment does not exist
             or is no longer effective

          -  Total bilirubin and aspartate aminotransferase (AST) levels consistent with normal
             hepatic function (total bilirubin and AST ≤ the upper limit of normal), moderate
             hepatic impairment (total bilirubin > 1.5 to 3x the upper limit of normal with any AST
             level) or severe hepatic impairment (total bilirubin > 3x the upper limit of normal
             with any AST level)

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

          -  Female patients who are postmenopausal for at least 1 year OR are surgically sterile
             OR if of childbearing potential, agree to practice 2 effective methods of
             contraception at the same time during the entire study through 90 days after the last
             dose of study drug OR agree to practice true abstinence

          -  Male patients who agree to practice effective barrier contraception during the entire
             study and through 90 days after the last dose of study drug OR agree to practice true
             abstinence

          -  Voluntary written consent

          -  Suitable venous access for the conduct of blood sampling

          -  Appropriate clinical laboratory values as specified in the protocol

        Exclusion Criteria:

          -  Systemic treatment with strong and moderate inhibitors of CYP1A2, strong and moderate
             inhibitors of CYP3A, or clinically significant CYP3A inducers or use of Ginkgo biloba
             or St. John's wort within 14 days before the first dose of study drug

          -  Use of any nicotine-containing products within 14 days before the first dose of study
             drug

          -  Central Nervous System Involvement or Symptomatic brain metastasis. Patients with
             brain metastases: must have stable neurologic status following local therapy (surgery
             or radiation) for at least 2 weeks after completion of the definitive therapy; and
             must be without neurologic dysfunction that would confound the evaluation of
             neurologic and other AEs

          -  Female patients who are lactating or breastfeeding or have a positive serum pregnancy
             test

          -  Serious medical or psychiatric illness that could interfere with participation in the
             study

          -  Treatment with any investigational products or radiotherapy within 21 days before the
             first dose of study drug

          -  Systemic anticancer therapy within 14 days before the first dose of study drug

          -  Exposure to nitrosoureas or mitomycin C within 6 weeks before the first dose of study
             drug

          -  Treatment with therapeutic monoclonal antibodies or antibody-drug conjugates within 60
             days before the first dose of study drug

          -  Radiotherapy or major surgery within the 14 days preceding the first dose of study
             drug

          -  Infection requiring systemic intravenous antibiotic therapy or other serious infection
             within 14 days before the first dose of study drug

          -  Life-threatening illness unrelated to cancer

          -  Severe CNS, pulmonary, or renal disease not related to the patient's cancer

          -  Known human immunodeficiency virus (HIV) positive

          -  Evidence of uncontrolled cardiovascular conditions

          -  QTc > 500 milliseconds (msec) on a 12-lead ECG obtained during the Screening period

          -  Known GI disease or GI procedure that could interfere with the oral absorption or
             tolerance of IXAZOMIB

          -  Known allergy to the study medication, its analogues, or excipients in the formulation