NCT00215605

Brief Summary

The purpose of this study is to determine the best and safest dose of XL184 administered orally. XL184 is a new chemical entity that inhibits VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration. To determine the highest safe dose, subjects will receive different amounts of the drug. The first group of subjects will receive the lowest dose of XL184. As long as no medically unacceptable side effects are noted, the dose will be increased for the next group. When the maximum tolerated dose (MTD) is reached, at least 20 subjects with Medullary Thyroid Cancer (MTC) will be enrolled to evaluate the effect of XL184 in this population.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
85

participants targeted

Target at P75+ for phase_1 lymphoma

Timeline
Completed

Started Sep 2005

Longer than P75 for phase_1 lymphoma

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2005

Completed
19 days until next milestone

First Submitted

Initial submission to the registry

September 20, 2005

Completed
2 days until next milestone

First Posted

Study publicly available on registry

September 22, 2005

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2011

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2012

Completed
Last Updated

February 27, 2013

Status Verified

February 1, 2013

Enrollment Period

5.6 years

First QC Date

September 20, 2005

Last Update Submit

February 26, 2013

Conditions

LymphomaCancerThyroid Carcinoma

Keywords

Advanced MalignanciesSolid TumorMedullary Thyroid Cancer

Outcome Measures

Primary Outcomes (2)

  • Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184

    Assessed during periodic visits

  • Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184

    Assessed during periodic visits

Secondary Outcomes (3)

  • Long-term safety/tolerability of XL184 after oral administration for up to 1 year

    Assessed during periodic visits

  • Evaluate preliminary tumor response after repeated XL184 administration

    Assessed during periodic visits

  • In MTD expanded cohort: Progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer

    Assessed during periodic visits

Study Arms (1)

1

EXPERIMENTAL
Drug: XL184

Interventions

XL184DRUG

Flavored liquid suspension or gelatin capsules supplied in 25-mg and 100-mg strengths; daily dosing or intermittent schedule (daily dosing followed by dosing holiday in cycles)

1

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed advanced malignancy (solid tumor or lymphoma) that is metastatic or unresectable for which standard curative measures do not exist or are no longer effective
  • Eastern Cooperative Oncology Group (ECOG) performance status \</= 2
  • Life expectancy greater than 3 months
  • Adequate organ and marrow function
  • Written informed consent
  • Use of acceptable methods of contraception during the course of the study and for 3 months after completion of study
  • In the MTD expanded cohort: at least 20 subjects with metastatic and/or advanced/locally recurrent Medullary Thyroid Cancer not appropriate for surgical resection with measurable disease as defined by RECIST

You may not qualify if:

  • Chemotherapy, immunotherapy or radiation within 4 weeks (or nitrosoureas or mitomycin C within 6 weeks) before the first scheduled dose of XL184
  • Administration of an investigational drug within 30 days of the first dose of XL184
  • Subject has not recovered from adverse events due to investigational agents or other medications administered more than 4 weeks before study enrollment
  • Known brain metastases
  • Uncontrolled intercurrent illness
  • Pregnancy or breastfeeding
  • Known HIV positive
  • Known allergy or hypersensitivity to any of the components of the XL184 formulation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

University of Chicago

Chicago, Illinois, 60637, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Univ. of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (3)

  • Kurzrock R, Atkins J, Wheler J, Fu S, Naing A, Busaidy N, Hong D, Sherman S. Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy. Ann Oncol. 2013 Sep;24(9):2256-61. doi: 10.1093/annonc/mdt177. Epub 2013 May 14.

    PMID: 23676418DERIVED

  • Kim KB, Cabanillas ME, Lazar AJ, Williams MD, Sanders DL, Ilagan JL, Nolop K, Lee RJ, Sherman SI. Clinical responses to vemurafenib in patients with metastatic papillary thyroid cancer harboring BRAF(V600E) mutation. Thyroid. 2013 Oct;23(10):1277-83. doi: 10.1089/thy.2013.0057. Epub 2013 Jul 17.

    PMID: 23489023DERIVED

  • Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Muller T, Ratain MJ, Salgia R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. doi: 10.1200/JCO.2010.32.4145. Epub 2011 May 23.

    PMID: 21606412DERIVED

MeSH Terms

Conditions

LymphomaNeoplasmsThyroid NeoplasmsCarcinoma, Medullary

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEndocrine Gland NeoplasmsNeoplasms by SiteHead and Neck NeoplasmsEndocrine System DiseasesThyroid DiseasesCarcinoma, NeuroendocrineNeuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms, Ductal, Lobular, and MedullaryNeoplasms, Nerve Tissue

Study Design

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

Study Record Dates

First Submitted

September 20, 2005

First Posted

September 22, 2005

Study Start

September 1, 2005

Primary Completion

April 1, 2011

Study Completion

July 1, 2012

Last Updated

February 27, 2013

Record last verified: 2013-02

Locations

US(5)