A Subject Treatment Preference Study of Tivozanib Versus Sunitinib in Subjects With Metastatic RCC

Study Overview
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Brief Summary
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Randomized, double-blind, 2-arm crossover study comparing tivozanib hydrochloride and sunitinib in subjects with metastatic RCC who have received no prior systemic therapy for Renal Cell Carcinoma (RCC).

Detailed Description
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This is a randomized, double-blind, 2-arm crossover study comparing tivozanib hydrochloride and sunitinib in subjects with metastatic RCC who have received no prior systemic therapy for Renal Cell Carcinoma (RCC). Approximately 160 subjects will be stratified for ECOG score (0 vs 1) and histology (clear cell vs non-clear cell) and then will be randomized 1:1 to 1 of 2 treatment arms. The study consists of two 12-week treatment periods with a 1-week washout in between. Subjects will receive double-blind (over-encapsulated) tivozanib hydrochloride and sunitinib sequentially. The study is designed to compare subject treatment preference, as well as overall safety and tolerability, frequency of dose modifications and kidney-specific health outcomes/QoL.

Official Title
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A Phase 2 Randomized, Double-Blind, Crossover, Controlled, Multi-Center Subject Preference Study of Tivozanib Hydrochloride Versus Sunitinib in the Treatment of Subjects With Metastatic Renal Cell Carcinoma

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Tivozanib
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable mRCC Histologically or cytologically confirmed RCC of any histology Subjects with or without prior nephrectomy Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Any prior systemic therapy for treatment of mRCC (including investigational or licensed drugs that target VEGF or VEGF receptors/pathway, or are mammalian target of rapamycin [mTOR] inhibitors) Central nervous system malignancies or metastases Significant hematologic, gastrointestinal, thromboembolic, vascular, bleeding, or coagulation disorders Significant serum chemistry or urinalysis abnormalities Significant cardiovascular disease, including symptomatic left ventricular ejection fraction or baseline LVEF of ≤ institutional lower limit of normal, uncontrolled hypertension, myocardial infarction or severe angina within 6 months prior to administration of first dose of study drug, history of class III or IV congestive heart failure, or history of serious ventricular arrhythmia, cardiac arrhythmias, or coronary or peripheral bypass graft within 6 months of screening Corrected QT interval (QTc) of >480 msec using Bazett's formula Currently active second primary malignancy

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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tivozanib Hydrochloride<br>1.5 mg oral tivozanib hydrochloride daily on a 3 weeks on/1 week off schedule for 12 weeks, followed by 50 mg oral sunitinib daily on a 4 weeks on/2 weeks off schedule for 12 weeks. | Drug: Tivozanib<br> <br> * Other names: Tivozanib Hydrochloride;|
| Active Comparator: Sunitinib<br>50 mg oral sunitinib daily on a 4 weeks on/2 weeks off schedule for 12 weeks, followed by 1.5 mg oral tivozanib hydrochloride daily on a 3 weeks on/1 week off schedule for 12 weeks. | Drug: Sunitinib<br> <br> * Other names: Sutent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Prefer Tivozanib Hydrochloride or Sunitinib | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With AEs and SAEs | Number of subjects with serious and non-serious adverse events. | Up to 25 weeks | 
| Number of Subjects With Dose Reductions | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Number of Subjects With Dose Interruptions | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Number of Subjects With Grade 3/4 Hematology Abnormalities | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Number of Subjects With Grade 3/4 Chemistry Abnormalities | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Number of Subjects With Grade 3/4 Coagulation Abnormalities | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Number of Subjects With Grade 3/4 Urinalysis Abnormalities | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Number of Subjects With Grade 3/4 Thyroid Function Abnormalities | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Up to 25 weeks | 
| Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | 
| Change From Baseline in FACT Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | 
| Change From Baseline in Functional Assessment of Cancer Therapy-Diarrhea (FACT-D) | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | 
| Change From Baseline in Euro Quality of Life - 5 Dimensions (EQ-5D) | The study was terminated prior to completing enrollment; due to low enrollment, no data was collected for this outcome measure. | Baseline, Weeks 1, 4, 10, 14, 17, 23, and End of Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tivozanib hydrochloride, renal cell carcinoma, subject preference, quality of life