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

September 17, 2013 updated by: Exelixis

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

The primary objective of this clinical study is to determine whether the inhibition of cytochrome P450 (CYP) isozyme CYP2C8 by XL184 observed in in vitro preclinical studies translates into the potential for clinically significant drug-drug interactions in humans. The study will measure the effect of once daily dosing of XL184 on the pharmacokinetics (PK) of rosiglitazone. The PK of XL184 when combined with rosiglitazone will be evaluated as well.

A specific objective of this study is to determine whether the interaction between XL184 and a drug such as rosiglitazone is sufficiently large enough to necessitate a dosage adjustment when used in combination with XL184, or whether the interaction would require additional therapeutic monitoring.

Rosiglitazone, commonly known as Avandia, is a prescription medicine approved by the FDA used to treat adults with Type 2 (adult-onset or non-insulin dependent) diabetes mellitus (high blood sugar). In this study, subjects will only take 2 doses of rosiglitazone. There is no intention of therapy as a result of taking rosiglitazone in this study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope Comprehensive Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • New York
      • Bronx, New York, United States, 10466
        • Montefiore Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
    • Texas
      • Houston, Texas, United States, 77230
        • The University of Texas M.D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: All subjects
All subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart
Drug: rosiglitazone
one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later
Other Names:
  • Avandia
Drug: XL184
dosed with capsules daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of XL184 and rosiglitazone
Time Frame: at weekly or twice-weekly visits for the first 4 weeks
To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone
at weekly or twice-weekly visits for the first 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety and tolerability of repeated administration of XL184
Time Frame: at weekly or twice-weekly visits, then every 4 weeks
To evaluate safety and tolerability of daily oral administration of XL184 and two single doses of rosiglitazone
at weekly or twice-weekly visits, then every 4 weeks
Pharmacokinetics of XL184 after co-administration of rosiglitazone
Time Frame: at weekly or twice-weekly visits for 4 weeks
To evaluate the plasma PK of XL184 after a single dose of rosiglitazone
at weekly or twice-weekly visits for 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Exelixis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

August 1, 2012

Study Registration Dates

First Submitted

March 22, 2010

First Submitted That Met QC Criteria

April 7, 2010

First Posted (Estimate)

April 9, 2010

Study Record Updates

Last Update Posted (Estimate)

September 19, 2013

Last Update Submitted That Met QC Criteria

September 17, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XL184-008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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