Study of XL184 (Cabozantinib) in Adults With Advanced Malignancies

Study Overview
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Brief Summary
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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.

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

Conditions
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Lymphoma, Cancer, Thyroid Carcinoma

Intervention / Treatment
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* Drug: XL184


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: XL184<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Malignancies, Solid Tumor, Medullary Thyroid Cancer