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

NCT ID: NCT01100619

Last Updated: 2013-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Papillary Thyroid Cancer Follicular Thyroid Cancer Huerthle Cell Thyroid Cancer Renal Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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All subjects

All subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart

Group Type EXPERIMENTAL

rosiglitazone

Intervention Type DRUG

one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later

XL184

Intervention Type DRUG

dosed with capsules daily

Interventions

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rosiglitazone

one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later

Intervention Type DRUG

XL184

dosed with capsules daily

Intervention Type DRUG

Other Intervention Names

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Avandia

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Exelixis

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Choueiri TK, Pal SK, McDermott DF, Morrissey S, Ferguson KC, Holland J, Kaelin WG, Dutcher JP. A phase I study of cabozantinib (XL184) in patients with renal cell cancer. Ann Oncol. 2014 Aug;25(8):1603-8. doi: 10.1093/annonc/mdu184. Epub 2014 May 14.

Reference Type DERIVED
PMID: 24827131 (View on PubMed)

Other Identifiers

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XL184-008

Identifier Type: -

Identifier Source: org_study_id