Dose-Finding Study of Cabozantinib (XL184) in Japanese Subjects With Advanced Cancer

Cancer Clinical Trial

Official title:

Phase 1 Multiple Ascending Dose Study of XL184 Monotherapy in Japanese Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01553656
• Other study ID #: XL184-014
• Status: Completed
• Phase: Phase 1
• First received: March 9, 2012
• Last updated: August 19, 2015
• Start date: February 2011
• Est. completion date: July 2015

Study information

• Verified date: August 2015
• Source: Exelixis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: July 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Select Inclusion Criteria:

• Subjects with advanced or metastatic solid tumors for whom the standard of care is ineffective or inappropriate.

• NSCLC expansion cohort subjects must have confirmed NSCLC (Stage IIIb or IV) and documented activating mutations.

• At least 4 weeks must have elapsed from the last anti-cancer therapy. At least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin.

• Have adequate bone marrow function, adequate liver function, and adequate renal function.

• Sexually active subjects (men and women of child-bearing potential (WOCBP)) must agree to use medically accepted barrier methods of contraception (eg, male or female condom) during the course of the study and for 4 months after the last dose of study drug(s), even if oral contraceptives are also used. All subjects of reproductive potential must agree to use both a barrier method and a second method of birth control. Women of childbearing potential (WOCBP) must have a negative pregnancy test at screening.

Select Exclusion Criteria:

• Symptomatic central nervous system (CNS) metastasis, or active CNS metastasis requiring medication.

• WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period and for 4 months after the last dose of investigational product.

• Women who are pregnant or breastfeeding.

• Sexually active fertile men not using effective birth control for the entire study period and for 4 months after the last dose of investigational product if their partners are WOCBP.

• Subjects who have uncontrolled intercurrent illness including, but not limited to, infection requiring systemic therapy, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled angina pectoris, uncontrolled peptic ulcer, cardiac arrhythmia requiring medication.

• Subjects who are HIV antibody positive, HBs antigen positive, and/or HCV antibody positive.

• Subjects with body cavity fluid retention which requires drainage.

• Subjects with any major surgery within 8 weeks prior to study enrollment.

• Subjects with major unhealed wounds or fracture.

• Subjects with a history or concurrent diagnosis of gastrointestinal perforation.

• Subjects with evidence of bleeding tendency or coagulopathy.

• Subjects with a history of thromboembolism.

• Subjects with a history of or concurrent pancreatitis.

• Exposure to any investigational drug within 30 days of enrollment.

• Subjects receiving radiation therapy or treatment with radionuclides within 6 to 2 weeks before first dose of XL184.

• NSCLC expansion cohorts: subjects must not be diagnosed with another malignancy within 2 years before first dose of XL184.

Study Design

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

Related Conditions & MeSH terms

• Cancer
• NSCLC
• Solid Tumors

Intervention

Drug:
• cabozantinib capsules
cabozantinib capsules administered as 25-mg and 100-mg strengths once-daily until disease progression
• cabozantinib tablets
cabozantinib tablets administered as 20-mg and 60-mg strengths once-daily until disease progression

Locations

Country	Name	City	State
Japan	The Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR)	Ariake	Koto
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Exelixis

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose	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.	Assessed in the clinic on Days 1 through 29	Yes
Secondary	Safety and tolerability of XL184	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.	From study start to October 2014	Yes
Secondary	Plasma Pharmacokinetics	Assess plasma pharmacokinetics of daily oral administration of XL184 from Treatment Day 1 to Day 29.	Assessed in the clinic from Day 1 through Day 29	No
Secondary	Tumor response (preliminary anti-tumor activity)	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 to October 2014	No