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

NCT01553656 | Completed Phase 1

• 1 other identifier: XL184-014
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 2

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.

Conditions

Solid Tumors; Cancer; NSCLC

Keywords

Advanced cancer; Metastatic; NSCLC

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Safety and tolerability of XL184

  From study start to October 2014

• Plasma Pharmacokinetics

  Assessed in the clinic from Day 1 through Day 29

• Tumor response (preliminary anti-tumor activity)

  Study start to October 2014

Study Arms (1)

Cabozantinib capsules and tablets

EXPERIMENTAL

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; Drug: cabozantinib tablets

Interventions

cabozantinib capsules DRUG

cabozantinib capsules administered as 25-mg and 100-mg strengths once-daily until disease progression

Also known as: XL184

Cabozantinib capsules and tablets

cabozantinib tablets DRUG

cabozantinib tablets administered as 20-mg and 60-mg strengths once-daily until disease progression

Also known as: XL184

Cabozantinib capsules and tablets

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Exelixis: lead

Study Sites (2)

The Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR)

Ariake, Koto, 135-8550, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Related Publications (1)

• 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.

  PMID: 30718102 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2012
• First Posted: March 14, 2012
• Study Start: February 1, 2011
• Primary Completion: May 1, 2015
• Study Completion: July 1, 2015
• Last Updated: August 20, 2015

Record last verified: 2015-08

Locations

JP (2)