A Drug-Drug Interaction Study of the Effects of XL184 (Cabozantinib) on Rosiglitazone in Subjects With Solid Tumors

Launched by EXELIXIS · Apr 7, 2010

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Eligibility criteria

• Inclusion Criteria:
• • 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 Discharge.
• Exclusion Criteria:
• • 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 study treatment.
• • 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 rosiglitazone) formulations.
• • 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 investigator.
• • 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.