Adjuvant Axitinib Therapy of Renal Cell Cancer in High Risk Patients

Study Overview
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Brief Summary
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The purpose of this trial is to determine if adjuvant therapy with axitinib will prevent or delay the recurrence of renal cell cancer after surgery to remove the primary tumor in high risk patients.

Detailed Description
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This is a prospective, randomized, double blind placebo controlled Phase 3 trial of oral axitinib starting at 5 mg twice daily given 3 years vs. placebo. Approximately 700 patients will be randomized in a 1:1 ratio between axitinib vs placebo.

Official Title
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Adjuvant Axitinib Treatment of Renal Cancer: A Randomized Double-blind Phase 3 Study of Adjuvant Axitinib vs. Placebo in Subjects at High Risk of Recurrent RCC

Conditions
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Clear Cell Renal Carcinoma

Intervention / Treatment
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* Drug: Axitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be treated by nephrectomy and patients must meet all of the following inclusion criteria to be eligible for enrollment into the trial: Patients must have no evidence of macroscopic residual disease or metastatic disease. Male or female, age >=18 years (age >=20 years in Japan, Korea and Taiwan). Patients must be diagnosed with one of the following based on American Joint Committee on Cancer (AJCC) TNM staging version 2010, Eastern Collaborative Oncology Group (ECOG) performance status (PS): pT2, pN0 or pNx, M0 and ECOG PS 0-1 pT3, pN0 or pNx, M0 and ECOG PS 0-1 pT4, pN0 or pNx, M0 and ECOG PS 0-1 Any pT, pN1, M0 and ECOG PS 0-1 Patients must have histologically confirmed preponderant, defined as >50%, clear cell RCC. Patients must not have received any previous systemic (includes chemotherapeutic, hormonal, or immunotherapeutic) treatment for RCC. Patients must not have received any previous anti angiogenic treatment. Patients must have adequate organ function. Exclusion Criteria Histologically undifferentiated carcinomas, sarcomas, collecting duct carcinoma, lymphoma, or patients with any metastatic renal sites. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 hemorrhage <4 weeks of date of randomization. Diagnosis of any non-RCC malignancy within the 5 years from date of randomization, 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. Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism. Gastrointestinal abnormalities

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Axitinib<br> | Drug: Axitinib<br>* Axitinib 5 mg twice daily<br>* Other names: Inlyta;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival (DFS) as Assessed by Blinded Independent Review Committee (IRC) | DFS is defined as time interval from the date of randomization to first date of recurrence/relapse (distant or local recurrence of [RCC] or occurrence of a secondary malignancy {occurrence of a second primary cancer other than RCC} or death). For participants with no DFS event, DFS was censored at date of last scan prior to time of analyses. Participants alive who did not have post-baseline disease assessments, DFS was censored at randomization. Participants who received further anti-tumor therapy prior to recurrence or occurrence of a secondary malignancy or death, DFS was censored on date of last scan prior to taking anti-tumor medication. Participants who missed 2 or more consecutive tumor scans immediately followed by an event were censored at date of last objective tumor assessment prior to missing/not readable scan. | From randomization date up to first date of recurrence or the occurrence of a secondary malignancy or death (up to 5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS defined as the time from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive. Participants lacking data beyond randomization had their survival times censored at randomization. | From randomization date until death due to any cause (up to 5 years) | 
| Number of Participants With Treatment-Emergent Adverse Events (AE) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious adverse events. | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 
| Number of Participants With Treatment-Emergent Treatment Related Adverse Events and Serious Adverse Events (SAEs) | A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events. | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE). | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 
| Number of Participants With Laboratory Abnormalities By Maximum CTCAE Grade: Hematology | Hematology parameters included anemia, hemoglobin increased, lymphocyte count increased, lymphocyte count decreased, neutrophil count decreased, platelet count decreased, and white blood cell count decreased. CTCAE grades: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE). | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 
| Number of Participants With Laboratory Abnormalities By Maximum CTCAE Grade: Chemistry | Chemistry parameters included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase increased, creatinine increased, hypoalbuminemia, hypercalcemia, hypocalcemia, hyperglycemia, hypoglycemia, hyperkalemia, hypokalemia, hypernatremia, hyponatremia. CTCAE grades: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE). | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 
| Number of Participants With Laboratory Abnormalities: Thyroid Function | Number of participants with thyrotropin levels: <5 milli-international units per litre (mIU/L), >=5 to <10 mIU/L, >=10 mIU/L are reported. | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 
| Number of Participants With Laboratory Abnormalities: Urinalysis | Number of participants with urine protein dipstick grading: negative/trace (5 to 20 milligram per deciliter [mg/dL]), 1+ (30 mg/dL]), 2+ (100 mg/dL), 3+ (300 mg/dL) and 4+ (more than 1000 mg/dL) are reported. | From Day 1 up to 28 days after last dose (maximum duration of 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal cell carcinoma, axitinib, tyrosine kinase inhibitor