Safety Study of PLX108-01 in Patients With Solid Tumors

A Phase 1 Study to Assess Safety, Pharmacokinetics, and Pharmacodynamics of PLX3397 in Patients With Advanced, Incurable, Solid Tumors in Which the Target Kinases Are Linked to Disease Pathophysiology

PLX3397 is a selective inhibitor of Fms, Kit, and oncogenic Flt3 activity. The primary objective of this study is to evaluate the safety and pharmacokinetics of orally administered PLX3397 in patients with advanced, incurable, solid tumors in which these target kinases are linked to disease pathophysiology. The secondary objective is to measure the pharmacodynamic activity of PLX3397 via blood, plasma and urine biomarkers of Fms activity.

Inclusion Criteria:

• Age 18 and older

• Solid tumors refractory to standard therapy

• For the Extension cohorts, patients must have measurable disease by RECIST criteria and meet the following disease-specific criteria:

  • For advanced or recurrent mucoepidermal carcinoma (MEC) of the salivary gland, patients must not be candidates for curative surgery or radiotherapy.
  • For pigmented villo-nodular synovitis (PVNS), patients must have a histologically confirmed diagnosis of inoperable progressive or relapsing PVNS, or resectable tumor requesting mutilating surgery, as well as demonstrated progressive disease in the last 12 months.
  • For gastrointestinal stromal tumors (GIST), patients must have failed previous therapy with imatinib and sunitinib. Patients with known PDGFR mutations are excluded, but mutation testing is not required for study entry.
  • For anaplastic thyroid cancer (ATC), patients must have histologically or cytologically diagnosed advanced ATC.
  • For metastatic solid tumors with documented malignant pleural and/or peritoneal effusions, patients must not be receiving specific therapy for the effusion or have an indwelling drain.

• Eastern Cooperative Oncology Group performance status 0 or 1

• Life expectancy >= 3 months

• Adequate hepatic, renal, and bone marrow function

Exclusion Criteria:

• Specific anti-cancer therapy within 3 weeks of study start
• Uncontrolled intercurrent illness
• Refractory nausea or vomiting, or malabsorption
• Mean corrected QT interval (QTc) >= 450 msec (for males) or QTc >= 470 msec (for females)