Back to resultsA Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Renal Cell Carcinoma
Primary Purpose
Advanced Renal Cell Carcinoma
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Cabozantinib
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Renal Cell Carcinoma focused on measuring Drug Therapy
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.
Sites / Locations
- Nagoya University Hospital
- Hokkaido University Hospital
- Sapporo Medical University Hospital
- Kobe University Hospital
- Yokohama City University Hospital
- Yokohama City University Medical Center
- Kindai University Hospital
- Osaka University Hospital
- Nippon Medcal School Hospital
- Toranomon Hospital
- Keio University Hospital
- Tokyo Women's Medical University Hospital
- Kyushu University Hospital
- Niigata University Medical and Dental Hospital
- Okayama University Hospital
- Osaka City University Hospital
- Osaka International Cancer Institute
- Tokushima University Hospital
- Yamagata University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Cabozantinib 60 mg
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Overall Survival (OS)
OS is defined as the time from the first day of study drug administration to death due to any cause.
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03339219
Brief Title
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
2. Study Status
Record Verification Date
August 2021
Overall Recruitment Status
Completed
Study Start Date
December 13, 2017 (Actual)
Primary Completion Date
August 25, 2020 (Actual)
Study Completion Date
August 25, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Renal Cell Carcinoma
Keywords
Drug Therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cabozantinib 60 mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cabozantinib
Other Intervention Name(s)
XL184
Intervention Description
Cabozantinib tablets
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
From first dose of study drug up to first documentation of CR or PR (up to 2.5 years)
Secondary Outcome Measure Information:
Title
Clinical Benefit Rate (CBR)
Description
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.
Time Frame
From first dose of study drug up to first documentation of CR or PR or SD (up to 2.5 years)
Title
Progression-Free Survival (PFS)
Description
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.
Time Frame
From first dose of study drug up to disease progression or death (up to 2.5 years)
Title
Overall Survival (OS)
Description
OS is defined as the time from the first day of study drug administration to death due to any cause.
Time Frame
From first dose of study drug up to death due to any cause (up to 2.5 years)
Title
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Title
Percentage of Participants With Grade 3 or Higher TEAEs
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Title
Percentage of Participants With Serious TEAEs
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Title
Percentage of Participants With TEAEs Leading to Permanent Treatment Discontinuation
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Title
Percentage of Participants With TEAEs Leading to Dose Modification (Dose Reduction or Interruption)
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Title
Percentage of Participants With Clinically Significant Abnormal Laboratory Values
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
Title
Percentage of Participants With Clinically Significant Abnormal Vital Sign
Description
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.
Time Frame
From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Nagoya University Hospital
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Hokkaido University Hospital
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Sapporo Medical University Hospital
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe
State/Province
Hyogo
Country
Japan
Facility Name
Yokohama City University Hospital
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Yokohama City University Medical Center
City
Yokohama
State/Province
Kanagawa
Country
Japan
Facility Name
Kindai University Hospital
City
Osakasayama
State/Province
Osaka
Country
Japan
Facility Name
Osaka University Hospital
City
Suita
State/Province
Osaka
Country
Japan
Facility Name
Nippon Medcal School Hospital
City
Bunkyo-ku
State/Province
Tokyo
Country
Japan
Facility Name
Toranomon Hospital
City
Minato-ku
State/Province
Tokyo
Country
Japan
Facility Name
Keio University Hospital
City
Shinjuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Tokyo Women's Medical University Hospital
City
Shinjuku-ku
State/Province
Tokyo
Country
Japan
Facility Name
Kyushu University Hospital
City
Fukuoka
Country
Japan
Facility Name
Niigata University Medical and Dental Hospital
City
Niigata
Country
Japan
Facility Name
Okayama University Hospital
City
Okayama
Country
Japan
Facility Name
Osaka City University Hospital
City
Osaka
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka
Country
Japan
Facility Name
Tokushima University Hospital
City
Tokushima
Country
Japan
Facility Name
Yamagata University Hospital
City
Yamagata
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Citations:
PubMed Identifier
32789967
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.
Results Reference
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A Phase 2 Study of Cabozantinib in Japanese Participants With Advanced Renal Cell Carcinoma
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