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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03339219

Enrollment

Registered

2017-11-13

Start date

2017-12-13

Completion date

2020-08-25

Last updated

2021-09-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced Renal Cell Carcinoma

Keywords

Drug Therapy

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.

Interventions

DRUGCabozantinib

Cabozantinib tablets

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate (ORR)	From first dose of study drug up to first documentation of CR or PR (up to 2.5 years)	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

Measure	Time frame	Description
Clinical Benefit Rate (CBR)	From first dose of study drug up to first documentation of CR or PR or SD (up to 2.5 years)	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)	From first dose of study drug up to disease progression or death (up to 2.5 years)	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)	From first dose of study drug up to death due to any cause (up to 2.5 years)	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)	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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)	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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	From first dose up to 30 days after the last dose of the study drug (up to 2.6 years)	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.

Countries

Japan

Participant flow

Recruitment details

Participants took part in the study at 16 investigative sites in Japan from 13 December 2017 to 25 August 2020.

Pre-assignment details

Participants with a diagnosis of advanced renal cell carcinoma (RCC) were enrolled in a single-arm study to receive cabozantinib 60 mg, tablet, orally, once daily.

Participants by arm

Arm	Count
Cabozantinib 60 mg 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.	35
Total	35

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	12
Overall Study	Site Terminated by Sponsor	22
Overall Study	Withdrawal by Subject	1

Baseline characteristics

Characteristic	Cabozantinib 60 mg	—
Age, Continuous	62.6 years STANDARD_DEVIATION 9.81	—
Eastern Cooperative Oncology (ECOG) Group PS Grade 0	26 Participants	—
Eastern Cooperative Oncology (ECOG) Group PS Grade 1	9 Participants	—
Heng Criteria Favorable Risk (0)	6 Participants	—
Heng Criteria Intermediate Risk (1-2)	22 Participants	—
Heng Criteria Poor Risk (3-6)	7 Participants	—
Karnofsky Performance Status (PS) 100 (Normal, no complaints, no evidence of disease)	24 Participants	—
Karnofsky Performance Status (PS) 70 (Cares for self, unable to carry on normal activity or to do active work)	1 Participants	—
Karnofsky Performance Status (PS) 80 (Normal activity with effort; some signs or symptoms of disease)	5 Participants	—
Karnofsky Performance Status (PS) 90 (Able to carry on normal activity; minor signs or symptoms of disease)	5 Participants	—
Memorial Sloan-Kettering Cancer Center (MSKCC) Risk Factors Favorable Risk (0)	11 Participants	—
Memorial Sloan-Kettering Cancer Center (MSKCC) Risk Factors Intermediate Risk (1)	19 Participants	—
Memorial Sloan-Kettering Cancer Center (MSKCC) Risk Factors Poor Risk (2 or 3)	5 Participants	—
Race and Ethnicity Not Collected	—	— Participants
Region of Enrollment Japan	35 Participants	—
Sex: Female, Male Female	11 Participants	—
Sex: Female, Male Male	24 Participants	—

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	12 / 35
other Total, other adverse events	35 / 35
serious Total, serious adverse events	15 / 35

Outcome results

Primary

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.

Time frame: From first dose of study drug up to first documentation of CR or PR (up to 2.5 years)

Population: FAS included all participants who received at least one dose of study drug.

Arm	Measure	Value (NUMBER)
Cabozantinib 60 mg	Objective Response Rate (ORR)	25.7 percentage of participants

Secondary

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.

Time frame: From first dose of study drug up to first documentation of CR or PR or SD (up to 2.5 years)

Population: FAS included all participants who received at least one dose of study drug.

Arm	Measure	Value (NUMBER)
Cabozantinib 60 mg	Clinical Benefit Rate (CBR)	85.7 percentage of participants

Secondary

Overall Survival (OS)

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)

Population: FAS included all participants who received at least one dose of study drug.

Arm	Measure	Value (MEDIAN)
Cabozantinib 60 mg	Overall Survival (OS)	NA months

Secondary

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.