Clinical trial NCT03339219: A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Renal Cell Carcinoma
Official title: A Phase 2, Open-Label, Single-Arm Study of Cabozantinib in Japanese Patients With Advanced Renal Cell Carcinoma That Has Progressed After Prior VEGFR Tyrosine Kinase Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Renal Cell Carcinoma
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-11-13
Enrollment: 35
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 efficacy of cabozantinib measured by Independent Radiology Committee (IRC)-assessed objective response rate (ORR) in Japanese participants with advanced renal cell carcinoma (RCC) that has progressed after prior vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) therapy.

Detailed description: The drug being tested in this study is called cabozantinib. Cabozantinib is being tested to treat people who have advanced renal cell carcinoma. This study will look at the efficacy of cabozantinib.

The study will enroll approximately 35 patients. Participants will be enrolled in one treatment group in non-randomized and opened manner:

• Cabozantinib 60 mg

All participants will be asked to take tablets of cabozantinib at once daily in the fasted state throughout the study.

This multi-center trial will be conducted in Japan. The overall time to participate in this study is approximately at most 3 years. Participants will make multiple visits to the clinic in treatment period, and posttreatment period including a follow-up assessment after last dose of study drug.

Eligibility criteria: Inclusion Criteria:

* Male or female Japanese participants 20 years of age or older on the day of consent.
* Documented histological or cytological diagnosis of renal cell carcinoma (RCC) with a clear-cell component.
* Measurable disease per RECIST 1.1 as determined by the investigator.
* Must have received at least one VEGFR-targeting TKI (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib).
* For the most recently received VEGFR-targeting TKI the following criteria must apply:

  * Must have radiographically progressed during treatment, or been treated for at least 4 weeks and radiographically progressed within 6 months after the last dose.

Radiographic progression is defined as unequivocal progression of existing tumor lesions or developing new tumor lesions as assessed by the investigator on computerized tomography (CT) or magnetic resonance imaging (MRI) scans.

- The last dose must have been within 6 months before the first day of study drug administration (Week 1 Day 1).

* Recovery to baseline or ≤Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
* Karnofsky Performance Status (KPS) score of ≥70%.
* Adequate organ and marrow function at Screening.

Exclusion Criteria:

* Prior treatment with everolimus, or any other specific or selective target of rapamycin complex 1/phosphoinositide 3-kinase/AKT inhibitor (eg, temsirolimus), or cabozantinib.
* Receipt of any type of small-molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before Week 1 Day 1.
* Receipt of any type of anticancer antibody (including investigational antibody) within 28 days before Week 1 Day 1.
* Radiation therapy for bone metastasis within 14 days, and/or any other external radiation therapy within 28 days before Week 1 Day 1. Systemic treatment with radionuclides within 42 days before Week 1 Day 1.

Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug up to first documentation of CR or PR (up to 2.5 years)
Secondary outcomes:
measure: Clinical Benefit Rate (CBR)
timeFrame: From first dose of study drug up to first documentation of CR or PR or SD (up to 2.5 years)
measure: Progression-Free Survival (PFS)
timeFrame: From first dose of study drug up to disease progression or death (up to 2.5 years)
measure: Overall Survival (OS)
timeFrame: From first dose of study drug up to death due to any cause (up to 2.5 years)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
measure: Percentage of Participants With Grade 3 or Higher TEAEs
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
measure: Percentage of Participants With Serious TEAEs
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
measure: Percentage of Participants With TEAEs Leading to Permanent Treatment Discontinuation
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
measure: Percentage of Participants With TEAEs Leading to Dose Modification (Dose Reduction or Interruption)
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
measure: Percentage of Participants With Clinically Significant Abnormal Laboratory Values
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
measure: Percentage of Participants With Clinically Significant Abnormal Vital Sign
timeFrame: From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Kobe
country: Japan
facility: Kobe University Hospital
state: Hyogo
city: Yokohama
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
state: Kanagawa
city: Osakasayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Bunkyo-ku
country: Japan
facility: Nippon Medcal School Hospital
state: Tokyo
city: Minato-ku
country: Japan
facility: Toranomon Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Keio University Hospital
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Tokyo Women's Medical University Hospital
state: Tokyo
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
city: Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka City University Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute
city: Tokushima
country: Japan
facility: Tokushima University Hospital
city: Yamagata
country: Japan
facility: Yamagata University Hospital
Study officials:
affiliation: Takeda
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Tomita Y, Tatsugami K, Nakaigawa N, Osawa T, Oya M, Kanayama H, Nakayama Kondoh C, Sassa N, Nishimura K, Nozawa M, Masumori N, Miyoshi Y, Kuroda S, Tanaka S, Kimura A, Tamada S. Cabozantinib in advanced renal cell carcinoma: A phase II, open-label, single-arm study of Japanese patients. Int J Urol. 2020 Nov;27(11):952-959. doi: 10.1111/iju.14329. Epub 2020 Aug 12.