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

NCT01100619 | Completed Phase 1

• 1 other identifier: XL184-008
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Safety and tolerability of repeated administration of XL184

  at weekly or twice-weekly visits, then every 4 weeks

• Pharmacokinetics of XL184 after co-administration of rosiglitazone

  at weekly or twice-weekly visits for 4 weeks

Study Arms (1)

All subjects

EXPERIMENTAL

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

Drug: rosiglitazone; Drug: XL184

Interventions

rosiglitazone DRUG

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

Also known as: Avandia

All subjects

XL184 DRUG

dosed with capsules daily

All subjects

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (5)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Montefiore Medical Center

The Bronx, New York, 10466, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77230, United States

Location

Related Publications (1)

• 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.

  PMID: 24827131 DERIVED

MeSH Terms

Conditions

Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Carcinoma, Renal Cell

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Thyroid Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2010
• First Posted: April 9, 2010
• Study Start: April 1, 2010
• Primary Completion: August 1, 2012
• Last Updated: September 19, 2013

Record last verified: 2013-09

Locations

US (5)