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

• ClinicalTrials.gov Identifier: NCT00375674
• Recruitment Status: Completed
• First Posted: September 13, 2006
• Results First Posted: August 18, 2017
• Last Update Posted: September 21, 2018
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: September 12, 2006
• First Posted Date: September 13, 2006
• Results First Submitted Date: February 22, 2017
• Results First Posted Date: August 18, 2017
• Last Update Posted Date: September 21, 2018
• Actual Study Start Date: August 1, 2007
• Actual Primary Completion Date: April 7, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 25, 2018)

• Disease-free Survival (DFS)- Assessed by Blinded Independent Central Review [ Time Frame: Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent.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 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for recurrence or occurrence of a secondary malignancy for remainder of follow-up period unless the participant had withdrawn consent.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.
• DFS- Assessed by the Investigator [Stratified by University of California Los Angeles Integrated Staging System (UISS) High Risk Group-Intent to Treat Population] [ Time Frame: Every 12 weeks during the first 3 years and every 6 months after that unless the participant had withdrawn consent.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 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.

• Original Primary Outcome Measures (submitted: September 12, 2006): Disease-free survival comparing sunitinib with placebo

Current Secondary Outcome Measures (submitted: July 25, 2018)

• Overall Survival (OS)- (Stratified by UISS High Risk Group-Intent to Treat Population) [ Time Frame: Every 12 weeks until the time for final analysis (up to data cut-off date: 30 April 2017; maximum exposure:14.9 months) ]
  OS was defined as the time from the date of randomization to the date of death due to any cause.
• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity [ Time Frame: 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 ]
  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.
• Summary of Duration of Treatment-Emergent Adverse Events of Special Interest by MedDRA Preferred Terms (All Causalities, All Cycles) [ Time Frame: 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 ]
  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.
• 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 [ Time Frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) ]
  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.
• PROs- EORTC QLQ C30: Functional Scale Scores Between Treatment Comparison [ Time Frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) ]
  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.
• PROs- EORTC QLQ-C30: Symptom Scale Scores Between Treatment Comparison [ Time Frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) ]
  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.
• PROs- EuroQoL EQ-5D Observed Means - Intent to Treat Population [ Time Frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) ]
  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.
• PROs- EuroQol European Quality of Life Questionnaire Variable Analogue Scale (EQ-VAS) Observed Means [ Time Frame: Cycle 1(Day 1); subsequent cycles (Day 1) and end of treatment/withdrawal (ie, up to 1 year) ]
  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).
• Number of Participants With Tolerability Symptoms [ Time Frame: 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 ]
  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.

• Original Secondary Outcome Measures (submitted: September 12, 2006): Relapse-free Survival Overall Survival Patient-reported outcomes Safety
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Clinical Trial Comparing Efficacy And Safety Of Sunitinib Versus Placebo For TheTreatment Of Patients At High Risk Of Recurrent Renal Cell Cancer
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Kidney Neoplasms

Intervention

• Drug: Sunitinib malate
  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.
• Other: Placebo
  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

Study Arms

• Experimental: A
  Intervention: Drug: Sunitinib malate
• Placebo Comparator: B
  Intervention: Other: Placebo

Publications *

• Patel A, Ravaud A, Motzer RJ, Pantuck AJ, Staehler M, Escudier B, Martini JF, Lechuga M, Lin X, George DJ. Exploratory analysis of the platelet-to-lymphocyte ratio prognostic value in the adjuvant renal cell cancer setting. Future Oncol. 2021 Feb;17(4):403-409. doi: 10.2217/fon-2020-0652. Epub 2020 Oct 8.
• Ouzaid I, Kammerer-Jacquet SF, Khene Z, Ravaud A, Patard JJ, Bensalah K, Rioux-Leclercq N. Exploring Biological Predictive Factors of Progression After Surgery in High-Risk Renal Cell Carcinoma: Results From the French Cohort of the Randomized S-TRAC Trial Patients. Front Surg. 2020 Jun 5;7:26. doi: 10.3389/fsurg.2020.00026. eCollection 2020.
• Staehler M, Motzer RJ, George DJ, Pandha HS, Donskov F, Escudier B, Pantuck AJ, Patel A, DeAnnuntis L, Bhattacharyya H, Ramaswamy K, Zanotti G, Lin X, Lechuga M, Serfass L, Paty J, Ravaud A. Adjuvant sunitinib in patients with high-risk renal cell carcinoma: safety, therapy management, and patient-reported outcomes in the S-TRAC trial. Ann Oncol. 2018 Oct 1;29(10):2098-2104. doi: 10.1093/annonc/mdy329.
• Rini BI, Escudier B, Martini JF, Magheli A, Svedman C, Lopatin M, Knezevic D, Goddard AD, Febbo PG, Li R, Lin X, Valota O, Staehler M, Motzer RJ, Ravaud A. Validation of the 16-Gene Recurrence Score in Patients with Locoregional, High-Risk Renal Cell Carcinoma from a Phase III Trial of Adjuvant Sunitinib. Clin Cancer Res. 2018 Sep 15;24(18):4407-4415. doi: 10.1158/1078-0432.CCR-18-0323. Epub 2018 May 17.
• George DJ, Martini JF, Staehler M, Motzer RJ, Magheli A, Escudier B, Gerletti P, Li S, Casey M, Laguerre B, Pandha HS, Pantuck AJ, Patel A, Lechuga MJ, Ravaud A. Immune Biomarkers Predictive for Disease-Free Survival with Adjuvant Sunitinib in High-Risk Locoregional Renal Cell Carcinoma: From Randomized Phase III S-TRAC Study. Clin Cancer Res. 2018 Apr 1;24(7):1554-1561. doi: 10.1158/1078-0432.CCR-17-2822. Epub 2018 Jan 26.
• Motzer RJ, Ravaud A, Patard JJ, Pandha HS, George DJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Casey M, Serfass L, Pantuck AJ, Staehler M. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results. Eur Urol. 2018 Jan;73(1):62-68. doi: 10.1016/j.eururo.2017.09.008. Epub 2017 Sep 28.
• Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ; S-TRAC Investigators. Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy. N Engl J Med. 2016 Dec 8;375(23):2246-2254. Epub 2016 Oct 9.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 19, 2017): 674
• Original Enrollment (submitted: September 12, 2006): 228
• Actual Study Completion Date: September 7, 2017
• Actual Primary Completion Date: April 7, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, China, Colombia, Czechia, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Poland, Slovakia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
• Removed Location Countries: Austria, Czech Republic

Administrative Information

• NCT Number: NCT00375674
• Other Study ID Numbers: A6181109; 2006-004024-37 ( EudraCT Number ); S-TRAC ( Other Identifier: Alias Study Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2018