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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01100619
Other study ID # XL184-008
Secondary ID
Status Completed
Phase Phase 1
First received March 22, 2010
Last updated September 17, 2013
Start date April 2010

Study information

Verified date September 2013
Source Exelixis
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

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.


Recruitment information / eligibility

Status Completed
Enrollment 40
Est. completion date
Est. primary completion date August 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
rosiglitazone
one 4 mg dose as a tablet followed by a second 4 mg dose 3 weeks later
XL184
dosed with capsules daily

Locations

Country Name City State
United States Dana Farber Cancer Institute Boston Massachusetts
United States Montefiore Medical Center Bronx New York
United States City of Hope Comprehensive Cancer Center Duarte California
United States The University of Texas M.D. Anderson Cancer Center Houston Texas
United States Hospital of the University of Pennsylvania Philadelphia Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Pharmacokinetics of XL184 and rosiglitazone 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 No
Secondary Safety and tolerability of repeated administration of XL184 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 Yes
Secondary Pharmacokinetics of XL184 after co-administration of rosiglitazone To evaluate the plasma PK of XL184 after a single dose of rosiglitazone at weekly or twice-weekly visits for 4 weeks No
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