Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies - Full Text View

Sponsor:	Exelixis
Information provided by:	Exelixis
ClinicalTrials.gov Identifier:	NCT00215605

Purpose

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.

Condition	Intervention	Phase
Lymphoma Cancer Thyroid Carcinoma	Drug: XL184	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma Thyroid Cancer Thyroid Diseases

U.S. FDA Resources

Further study details as provided by Exelixis:

Primary Outcome Measures:

Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184 [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: Yes ]
Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184 [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Long-term safety/tolerability of XL184 after oral administration for up to 1 year [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: Yes ]
Evaluate preliminary tumor response after repeated XL184 administration [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]
In MTD expanded cohort: Progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer [ Time Frame: Assessed during periodic visits ] [ Designated as safety issue: No ]

Estimated Enrollment:	77
Study Start Date:	September 2005
Estimated Study Completion Date:	August 2011
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: XL184 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)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00215605

Locations

United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21231
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10021
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Texas
Univ. of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

Exelixis

More Information

No publications provided by Exelixis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Müller 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. Epub 2011 May 23.

Responsible Party:	John Frye, PharmD/Senior Director, Clinical Science, Exelixis, Inc.
ClinicalTrials.gov Identifier:	NCT00215605 History of Changes
Obsolete Identifiers:	NCT00354289
Other Study ID Numbers:	XL184-001
Study First Received:	September 20, 2005
Last Updated:	June 2, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Exelixis:

Advanced Malignancies
Solid Tumor
Medullary Thyroid Cancer

Additional relevant MeSH terms:

Neoplasms
Carcinoma
Thyroid Neoplasms
Lymphoma
Thyroid Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms

Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on February 09, 2012