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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Exelixis
ClinicalTrials.gov Identifier:
NCT01100619
First received: March 22, 2010
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Papillary Thyroid Cancer
Follicular Thyroid Cancer
Huerthle Cell Thyroid Cancer
Renal Cell Carcinoma
Drug: rosiglitazone
Drug: XL184
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Exelixis:

Primary Outcome Measures:
  • Pharmacokinetics of XL184 and rosiglitazone [ Time Frame: at weekly or twice-weekly visits for the first 4 weeks ] [ Designated as safety issue: No ]
    To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone


Secondary Outcome Measures:
  • Safety and tolerability of repeated administration of XL184 [ Time Frame: at weekly or twice-weekly visits, then every 4 weeks ] [ Designated as safety issue: Yes ]
    To evaluate safety and tolerability of daily oral administration of XL184 and two single doses of rosiglitazone

  • Pharmacokinetics of XL184 after co-administration of rosiglitazone [ Time Frame: at weekly or twice-weekly visits for 4 weeks ] [ Designated as safety issue: No ]
    To evaluate the plasma PK of XL184 after a single dose of rosiglitazone


Enrollment: 40
Study Start Date: April 2010
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Avandia
Drug: XL184
dosed with capsules daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01100619

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

No publications provided

Responsible Party: Exelixis
ClinicalTrials.gov Identifier: NCT01100619     History of Changes
Other Study ID Numbers: XL184-008
Study First Received: March 22, 2010
Last Updated: September 17, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Thyroid Neoplasms
Carcinoma, Renal Cell
Thyroid Diseases
Adenocarcinoma, Follicular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 28, 2014