Clinical trial NCT01553656: Dose-Finding Study of Cabozantinib (XL184) in Japanese Subjects With Advanced Cancer
Official title: Phase 1 Multiple Ascending Dose Study of XL184 Monotherapy in Japanese Subjects With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Cancer
NSCLC
Keywords: Advanced cancer
Metastatic
NSCLC
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2012-03-14
Enrollment: 85
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility 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.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose
timeFrame: Assessed in the clinic on Days 1 through 29
Secondary outcomes:
measure: Safety and tolerability of XL184
timeFrame: From study start to October 2014
measure: Plasma Pharmacokinetics
timeFrame: Assessed in the clinic from Day 1 through Day 29
measure: Tumor response (preliminary anti-tumor activity)
timeFrame: Study start to October 2014
Other outcomes:
Locations:
city: Ariake
country: Japan
facility: The Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR)
state: Koto
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
Study officials:
References:
citation: Nokihara H, Nishio M, Yamamoto N, Fujiwara Y, Horinouchi H, Kanda S, Horiike A, Ohyanagi F, Yanagitani N, Nguyen L, Yaron Y, Borgman A, Tamura T. Phase 1 Study of Cabozantinib in Japanese Patients With Expansion Cohorts in Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2019 May;20(3):e317-e328. doi: 10.1016/j.cllc.2018.12.018. Epub 2018 Dec 31.