A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Renal Cell Carcinoma

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Advanced Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Cabozantinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cabozantinib 60 mg<br>Cabozantinib 60 mg, tablet, orally, once daily (QD) in the fasted state until unacceptable toxicity or need for subsequent systemic anticancer treatment up to 2.5 years. | Drug: Cabozantinib<br>* Cabozantinib tablets<br>* Other names: XL184;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants whose best overall response was complete response (CR) or partial response (PR) evaluated by the independent review committee (IRC) per response evaluation criteria in solid tumors version 1.1 (RECIST V1.1) which was confirmed by a subsequent evaluation conducted ≥28 days later. Per RECIST V1.1, CR was defined as the disappearance of all lesions, and all pathological lymph nodes (whether target or nontarget) must have a reduction in short axis to <10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameter (SoD) of target lesions, taking as a reference the Baseline SoD. | From first dose of study drug up to first documentation of CR or PR (up to 2.5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate (CBR) | CBR was defined as percentage of participants whose best overall response is CR, PR, or stable disease (SD) per RECIST V1.1. Response and progression were evaluated by IRC per RECIST V1.1. CR and PR required confirmation by a subsequent evaluation conducted ≥28 days later and an assessment of SD was made at least 8 weeks after the first day of study drug. Per RECIST V1.1, CR was defined as the disappearance of all lesions, and all pathological lymph nodes (whether target or nontarget) must have a reduction in the short axis to <10 mm. PR was defined as at least a 30% decrease in SoD of target lesions, taking as a reference the Baseline SoD. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. | From first dose of study drug up to first documentation of CR or PR or SD (up to 2.5 years) | 
| Progression-Free Survival (PFS) | PFS was defined as the time from the first day of study drug administration to the earlier of progressive disease (PD) per RECIST V1.1 or death due to any cause. Per RECIST V1.1, PD was defined at least a 20% increase in the SoD of target lesions, taking as a reference the smallest (nadir) SoD since (and including) Baseline. In addition to the relative increase of 20%, the SoD also demonstrated an absolute increase of at least 5 mm. | From first dose of study drug up to disease progression or death (up to 2.5 years) | 
| Overall Survival (OS) | OS is defined as the time from the first day of study drug administration to death due to any cause. | From first dose of study drug up to death due to any cause (up to 2.5 years) | 
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as AEs whose date of onset occurs on or after the start of study drug and within 30 days after the last dose of study treatment. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 
| Percentage of Participants With Grade 3 or Higher TEAEs | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as AEs whose date of onset occurs on or after the start of study drug and within 30 days after the last dose of study treatment. Severity grade was defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. As per the NCI-CTCAE, Grade 1 scales as mild; Grade 2 scales as moderate; Grade 3 scales as severe or medically significant but not immediately life-threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 
| Percentage of Participants With Serious TEAEs | A serious TEAE was any untoward medical occurrence or effect that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was medically important due to other reasons than the above-mentioned criteria. TEAEs were defined as AEs whose date of onset occurs on or after the start of study drug and within 30 days after the last dose of study treatment. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 
| Percentage of Participants With TEAEs Leading to Permanent Treatment Discontinuation | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as AEs whose date of onset occurs on or after the start of study drug and within 30 days after the last dose of study treatment. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 
| Percentage of Participants With TEAEs Leading to Dose Modification (Dose Reduction or Interruption) | An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAEs were defined as AEs whose date of onset occurs on or after the start of study drug and within 30 days after the last dose of study treatment. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 
| Percentage of Participants With Clinically Significant Abnormal Laboratory Values | Clinical laboratory tests included tests of serum chemistry, hematology, urine chemistry, coagulation, and thyroid function prespecified in the protocol. Only those categories are reported which are considered clinically significant abnormal laboratory values post baseline, as assessed by the investigator. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 
| Percentage of Participants With Clinically Significant Abnormal Vital Sign | Vital signs included diastolic blood pressure (DBP) and systolic blood pressure (SBP) in the sitting position, pulse rate respiratory rate temperature, and weight. Abnormal vital sign values considered by the investigator to be clinically significant are reported as categories. | From first dose up to 30 days after the last dose of the study drug (up to 2.6 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug Therapy