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Papillary Thyroid CancerPhase 1NCT01100619

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

A Phase 1 study testing rosiglitazone and XL184 in people with Papillary Thyroid Cancer and Follicular Thyroid Cancer, run by Exelixis at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rosiglitazone and XL184
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
5 sitesUnited States
Study dates
Apr 2010to Aug 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • The University of Texas M.D. Anderson Cancer Center

    Houston, Texas, 77230

  • Hospital of the University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Montefiore Medical Center

    The Bronx, New York, 10466

Other trials in United States

About this study

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

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.

Being tested
rosiglitazone, XL184
Medical subject headings
Thyroid Cancer, Papillary, Adenocarcinoma, Follicular, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • rosiglitazoneDrug

    Also called Avandia

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

  • XL184Drug

    dosed with capsules daily

Study groups in NCT01100619
Study groupRoleWhat they receive
All subjectsExperimentalAll subjects will receive daily XL184, and two single doses of rosiglitazone, 3 weeks apart
Receives: Drug: rosiglitazone; Drug: XL184

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics of XL184 and rosiglitazone

    To evaluate the effect of multiple daily doses of XL184 on single dose PK of rosiglitazone

    Measured: at weekly or twice-weekly visits for the first 4 weeks

Secondary outcomes (2)

  1. 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

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

  2. Pharmacokinetics of XL184 after co-administration of rosiglitazone

    To evaluate the plasma PK of XL184 after a single dose of rosiglitazone

    Measured: at weekly or twice-weekly visits for 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionAug 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01100619
Sponsor's protocol ID
XL184-008
Status last verified
Sep 2013
First submitted
22 Mar 2010
Last updated
19 Sep 2013
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 24827131

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing rosiglitazone and XL184 in people with Papillary Thyroid Cancer and Follicular Thyroid Cancer, run by Exelixis at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics of XL184 and rosiglitazone (time frame: at weekly or twice-weekly visits for the first 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01100619, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2013.

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