A Phase 1 Drug-Drug Interaction Study of the Effects of XL184 on the Pharmacokinetics of a Single Oral Dose of Rosiglitazone in Subjects With Solid Tumors
- Diagnosis of a solid tumor that is metastatic or unresectable and is refractory to or
progressed (or relapsed) following standard therapies, or a disease for which no
standard therapy exists. Initial enrollment will be limited to differentiated thyroid
cancer and renal cell carcinoma. Additional criteria will apply.
- One lesion that is not within a previously radiated field and is measurable on
computerized tomography (CT), magnetic resonance imaging (MRI) scan.
- Body mass index (BMI) between 18 and 33 kg/m2.
- Karnofsky Performance Status (≥ 70).
- Adequate organ and marrow function.
- Able to reside in the clinic for two one-day confinement periods in their entirety.
- The subject is willing to refrain from consuming CYP-interacting foods including
Seville orange-containing products, grapefruit-containing products, and star
fruit-containing products, from 72 hours prior to first dose through the Day 23
- Restrictions regarding certain prior treatments will apply.
- The subject has experienced clinically-significant hematemesis or hemoptysis of > 2.5
ml of red blood within 28 days prior to the first dose of study treatment, or other
signs indicative of pulmonary hemorrhage within 28 days prior to the first dose of
- Not recovered from toxicity due to all prior therapies (ie, return to pre-therapy
baseline or Grade ≤ 1).
- Primary brain tumor or brain metastases or spinal cord compression, unless completed
radiation therapy ≥ 28 days prior to study. treatment or had surgical resection and
is stable without steroid and without anti-convulsant treatment for ≥ 10 days.
- Prothrombin time/International Normalized Ratio (PT/INR) or partial thromboplastin
time (PTT) at screening ≥ 1.5 times the laboratory upper limit of normal.
- Uncontrolled, significant intercurrent illness.
- Inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- Pregnancy or breastfeeding.
- Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C.
- Allergy or hypersensitivity to components of either of the study treatment (XL184 and
- History of any medical or surgical conditions (eg, stomach or intestinal surgery or
resection) that would potentially interfere with or alter the gastrointestinal (GI)
absorption, distribution, metabolism, or excretion of the study drug (exceptions:
appendectomy, hernia repair, and/or cholecystectomy will be allowed).
- History of, or clinical evidence of, pancreatic injury or pancreatitis, including but
not limited to having amylase or lipase levels outside of normal limits.
- Hepatic impaired, ie, with a Child-Pugh score of B or C.
- The subject is being treated with drug(s) that are known to be either extensively
metabolized by CYP2C8 (for example rosiglitazone), or inhibitors of either CYP2C8 or
CYP3A4, or inducers of CYP3A isozymes.
- The subject has used any prohibited prescription medications or products prior to the
first Check-in, or is unable or unwilling to forgo the use of such products from the
first Check-in through the Day 23 Discharge, unless deemed acceptable by the
- Poor peripheral venous access.
- The subject is receiving warfarin (or other coumarin derivatives) at study entry and
unable to switch to low molecular weight heparin.
- The subject is receiving dialysis.