Dose-Finding Study of Cabozantinib (XL184) in Japanese Subjects With Advanced Cancer
The purpose of this study is to evaluate the safety profile, tolerability, pharmacokinetics (PK), pharmacodynamics, pharmacogenomic (PGX) and preliminary efficacy following daily oral doses of cabozantinib (XL184) in Japanese patients with advanced or metastatic solid tumors. Also, the effect of XL184 in the treatment of non-small cell lung cancer (NSCLC) patients with various activating mutations will be evaluated at the recommended Phase 2 dose.
Drug: cabozantinib capsules
Drug: cabozantinib tablets
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Multiple Ascending Dose Study of XL184 Monotherapy in Japanese Subjects With Advanced or Metastatic Solid Tumors|
- Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose [ Time Frame: Assessed in the clinic on Days 1 through 29 ] [ Designated as safety issue: Yes ]To establish the MTD and recommended Phase 2 dose (or dose range as appropriate) of XL184 when administered orally on a once daily schedule in subjects with advanced or metastatic solid tumors.
- Safety and tolerability of XL184 [ Time Frame: From study start to October 2014 ] [ Designated as safety issue: Yes ]Safety and tolerability of multiple doses of XL184 administered orally on a daily basis. Assessed from informed consent until at least 30 days after discontinuation.
- Plasma Pharmacokinetics [ Time Frame: Assessed in the clinic from Day 1 through Day 29 ] [ Designated as safety issue: No ]Assess plasma pharmacokinetics of daily oral administration of XL184 from Treatment Day 1 to Day 29.
- Tumor response (preliminary anti-tumor activity) [ Time Frame: Study start to October 2014 ] [ Designated as safety issue: No ]Assess tumor response after repeated administration of XL184 from screening until discontinuation. Assessed as best overall response by cohort by radiological response defined by RECIST criteria.
|Study Start Date:||February 2011|
|Estimated Study Completion Date:||November 2014|
|Estimated Primary Completion Date:||October 2014 (Final data collection date for primary outcome measure)|
Experimental: Cabozantinib capsules and tablets
Subjects will be enrolled in cohorts at different dose levels in order to determine the maximum tolerated dose of cabozantinib. Initially, subjects enrolled will receive the capsule formulation; other subjects will receive the tablet formulation.
Drug: cabozantinib capsules
cabozantinib capsules administered as 25-mg and 100-mg strengths once-daily until disease progression
Other Name: XL184Drug: cabozantinib tablets
cabozantinib tablets administered as 20-mg and 60-mg strengths once-daily until disease progression
Other Name: XL184
|Contact: Exelixis Clinical Trials||1-888-393-5494|
|Contact: Backup or International||+1-650-837-7400|
|The Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR)||Recruiting|
|Ariake, Koto, Japan, 135-8550|
|Principal Investigator: Makoto Nishio, MD|
|National Cancer Center Hospital||Recruiting|
|Chuo-ku, Tokyo, Japan, 104-0045|
|Principal Investigator: Tomohide Tamura, MD|