Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies

Cancer Clinical Trial

Official title:

A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL184 Administered Orally to Subjects With Advanced Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00215605
• Other study ID #: XL184-001
• Status: Completed
• Phase: Phase 1
• First received: September 20, 2005
• Last updated: February 26, 2013
• Start date: September 2005
• Est. completion date: July 2012

Study information

• Verified date: February 2013
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00354289

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: July 2012
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer
• Lymphoma
• Thyroid Carcinoma
• Thyroid Neoplasms

Intervention

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)

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	University of Chicago	Chicago	Illinois
United States	Univ. of Texas MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety, tolerability, maximum tolerated dose (MTD), and dose-limiting toxicity of oral administration of XL184		Assessed during periodic visits	Yes
Primary	Evaluate plasma pharmacokinetics and estimate renal elimination of oral administration of XL184		Assessed during periodic visits	No
Secondary	Long-term safety/tolerability of XL184 after oral administration for up to 1 year		Assessed during periodic visits	Yes
Secondary	Evaluate preliminary tumor response after repeated XL184 administration		Assessed during periodic visits	No
Secondary	In MTD expanded cohort: Progression-free survival and duration of response in subjects with advanced or recurrent medullary thyroid cancer		Assessed during periodic visits	No