A Clinical Trial Comparing Efficacy And Safety Of Sunitinib Versus Placebo For TheTreatment Of Patients At High Risk Of Recurrent Renal Cell Cancer

Study Overview
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Brief Summary
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To compare the disease free survival time and safety of sunitinib with placebo in adjuvant treatment patients at high risk of recurrent kidney cancer after surgery.

Official Title
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Sunitinib Treatment Of Renal Adjuvant Cancer (S-trac): A Randomized Double-blind Phase 3 Study Of Adjuvant Sunitinib Vs. Placebo In Subjects At High Risk Of Recurrent Rcc

Conditions
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Kidney Neoplasms

Intervention / Treatment
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* Drug: Sunitinib malate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: High risk renal cancer per modified UISS criteria Eastern Cooperative Oncology Group (ECOG) 0-2 predominant clear cell histology No prior anti-cancer treatment Kidney tumor has been removed No evidence of macroscopic disease following surgery Exclusion Criteria: Histologically undifferentiated carcinomas or collecting duct carcinoma, lymphoma, sarcoma or subjects with metastatic renal sites. Diagnosis of any second malignancy within the last 5 years, except basal cell carcinoma, squamous cell skin cancer, or in situ carcinoma of the cervix uteri that has been adequately treated with no evidence of recurrent disease for 12 months known HIV or Hepatitis any severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Sunitinib malate<br>* sunitinib malate 50 mg PO on schedule 4/2: 4 weeks on, 2 weeks off for 1 year or until disease recurrence or occurrence of a secondary malignancy, significant toxicity, or withdrawal of consent.<br>|
| Placebo Comparator: B<br> | Other: Placebo<br>* Placebo PO for 1 year on schedule 4/2: 4 weeks on, 2 weeks off or until disease recurrence or occurrence of a secondary malignancy, significant toxicity, or withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review | DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by blinded independent central review (BICR) or investigator assessment for respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for remainder of follow-up period unless the participant had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized. | Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later. | 
| DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population] | DFS was defined as the time interval (in years) from the date of randomization to the first date of recurrence or occurrence of a secondary malignancy or death. Recurrence refers to relapse of the primary tumor in-situ or at metastatic sites. Date of recurrence or occurrence: The date of the recurrence or occurrence of a secondary malignancy for the first time, either by BICR or investigator assessment for the respective analyses. Participants were followed with tumor imaging for recurrence or occurrence of a secondary malignancy for the remainder of the follow-up period unless the participants had withdrawn consent. According to the statistical analysis plan there are two cohorts: 1.Global Cohort: primary analysis of DFS was performed approximately 5 years after last participant in the Global Cohort is randomized; 2. China Cohort: primary analysis of DFS was performed approximately 3 years after the last participant in China Cohort was randomized. | Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent. Performed 5 years after LSLV or when approximately 258 events survival status, whichever was later | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population) | OS was defined as the time from the date of randomization to the date of death due to any cause. | Every 12 weeks until the time for final analysis (up to data cut-off date: 30 April 2017; maximum exposure:14.9 months) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity | TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. | Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later | 
| Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) | TEAEs are all AEs (serious and non-serious) occurred, for the first time, on or after the first day of study treatment. AEs started before the first dose of study treatment but increased in severity (CTC grade) over the baseline will also be considered TEAEs. Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. | Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later | 
| Patient-Reported Outcomes (PROs)- European Organization for Research and Treatment of Cancer (EORTC) QLQ C30: Observed Means in Global Health Status / Quality of Life Scale Scores | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale, 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess functioning & symptoms; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL & more severe for symptoms. | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | 
| PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), which was a 30-item questionnaire with global QoL scale & 5 multi-item functional scales (physical, role, emotional, cognitive, & social functioning). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess functioning; 2 items with 7-point Likert scales for global health & overall QoL. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented better level for functioning/QoL. | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | 
| PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison | PROs assessed health-related QoL by using the EORTC QLQ-C30, which was a 30 multi-item symptom scales (fatigue, nausea/vomiting, & pain), and 6 single item symptom scales for other cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, & the financial impact of cancer). The questionnaire includes 28 items with 4-point Likert type responses from not at all to very much to assess symptoms. All responses were converted to a 0 to 100 scale using a standard scoring algorithm, higher scores represented more severe symptoms. | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | 
| PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. In this outcome measure, the first part with 5 descriptors of current health state (mobility, self-care, usual activities, pain/discomfort, & anxiety/depression) was used; a participant was asked to rate each state on a 3-level scale (1=no problem, 2=some problem, & 3=extreme problem); higher levels indicated greater severity/impairment. The published weights allowed the creation of a single summary score called the EQ-5D index, which ranged from -0.594 to 1; low scores represented a higher level of dysfunction & 1 as perfect health. | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | 
| PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means | Patient-reported outcomes (PROs) assessed health-related quality of life (QoL) by the EuroQoL Group health status questionnaire (EQ-5D), which was a brief self-administered, validated instrument with 2 parts. The first part assessed the current health state. In this outcome measure, the second part was applied to assess the general health status by using visual analog scale (EQ-5D VAS) which measured participant's self-rated health status on a scale ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). | Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) | 
| Number of Participants With Tolerability Symptoms | Participants were followed for AEs from the first day of study treatment until at least 28 days after the last on-study treatment administration, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later. The treatment was administered to the participants from cycle1/day 1 up to 9 cycles or until relapse, secondary malignancy, death or withdraw for other reasons such as toxicity or withdraw of consent. This table provides the summary of discontinuations de to adverse events. Participants were counted only once in each row. | Cycle 1(Day 1 & Day 28); subsequent cycles (Day 1); end of treatment/withdrawal and 28 days post treatment, or until all serious or study medication-related toxicities had resolved or were determined to be chronic or stable, whichever was later |