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

Exelixis

Status and phase: Completed; Phase 1

Conditions: Cancer; Solid Tumors; NSCLC

Treatments: Drug: cabozantinib tablets; Drug: cabozantinib capsules

Study type: Interventional

Funder types: Industry

Identifiers

NCT01553656

XL184-014

Details and patient eligibility

About

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.

Enrollment: 85 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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85 participants in 1 patient group

Cabozantinib capsules and tablets

Experimental group

Description:

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.

Treatment:

Drug: cabozantinib capsules

Drug: cabozantinib tablets