Study of Pexidartinib in Asian Subjects With Advanced Solid Tumors
Condition: Advanced Solid Tumors
MeSH terms: Neoplasms
Intervention: Pexidartinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Advanced solid tumors; Asian subjects; Developmental Phase I

Summary:

      This is a Phase I, non-randomized, open-label, multiple dose study of pexidartinib in Asian
      subjects with advanced solid tumors. The study will be conducted in a dose escalation to
      assess the safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and
      preliminary antitumor activity of pexidartinib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age should be ≥ 20 years

          -  Subjects must have a pathologically documented solid tumor that has relapsed from, or
             is refractory to standard treatment, or for which no standard treatment is available

          -  All associated toxicity from previous cancer therapy must have been resolved (to ≤
             Grade 1) prior to administration of pexidartinib

          -  Eastern Cooperative Oncology Group (ECOG) score of 0 or 1

          -  Adequate hematologic, hepatic, and renal function tests

          -  Adequate treatment washout period before registration defined as:

               1. Major surgery: ≥ 4 weeks (2 weeks for less invasive surgery, such as colostomy)

               2. Radiation therapy (eg, whole brain radiotherapy): ≥ 4 weeks (if palliative
                  stereotactic radiation therapy, ≥ 2 weeks)

               3. Chemotherapy or immunotherapy (including targeted therapy with antibody or small
                  molecule, retinoid therapy, and hormonal therapy): 4 weeks or 5 half-lives of the
                  agent, whichever is shorter (if the regimen has contained nitrosoureas or
                  mitomycin C, ≥ 6 weeks)

               4. Other investigational drug therapy: ≥ 4 weeks

        Exclusion Criteria:

          -  Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant
             small bowel resection that would have precluded adequate absorption

          -  Previous use of pexidartinib or any biologic treatment targeting colony stimulating
             factor-1 (CSF-1) or the receptor for colony-stimulating factor-1 (CSF1R); previous use
             of oral tyrosine kinase inhibitors, eg, imatinib or nilotinib, is allowed

          -  Clinically active primary central nervous system tumors or brain metastasis, defined
             as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to
             control associated symptoms

          -  Active or chronic infection with hepatitis C or known positive hepatitis B surface.
             antigen, or known active or chronic infection with human immunodeficiency virus

          -  A screening Fridericia-corrected time between the start of the Q wave and the end of
             the T wave in the heart's electrical cycle (QTcF) ≥ 450 ms (in men) or ≥ 470 ms (in
             women).

          -  A medical history or complications of clinically significant lung disease (eg,
             interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation
             pneumonitis)

          -  A history of symptomatic congestive heart failure (CHF) [New York Heart Association
             (NYHA) Classes II to IV] or serious cardiac arrhythmia requiring treatment

          -  A history of myocardial infarction or unstable angina within 6 months before
             enrollment

          -  An uncontrolled infection requiring intravenous injection of antibiotics, antivirals,
             or antifungals