Biomarker Study of Pts With Metastatic ccRCC Undergoing Sequential Therapy With 1st Line Sunitinib and 2nd Line Axitinib

Study Overview
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Brief Summary
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This is a prospective single arm phase II study to evaluate potential prognostic and/or predictive biomarkers in patients with metastatic ccRCC undergoing treatment with 1st line sunitinib on a 4/2 schedule followed by axitinib on 2nd line therapy.

Detailed Description
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In this study, all included patients will receive sunitinib until disease progression and/or limiting toxicity. If patients develop toxicities ≥ Grade 2 on 50 mg per day 4 weeks-on / 2 weeks-off schedule, a modified schedule of 50 mg/day 2 weeks-on / 1 week-off will be offered. After disease progression on sunitinib, all eligible patients will receive axitinib 5 mg twice a day. The investigators plan to assess, by next generation sequencing, the prevalence of mutations in several cancer related genes in baseline archived tissue from the patients included in the study, and the potential correlations between these somatic mutations and anti-VEGF (Vascular Endothelial Growth Factor) therapy efficacy.

Official Title
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Biomarker Study of Patients With Metastatic Clear Cell Renal Carcinoma (ccRCC) Undergoing Sequential Therapy With 1st Line Sunitinib and 2nd Line Axitinib

Conditions
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Clear Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Locally advanced (defined as disease not amenable to curative surgery or radiation therapy) or metastatic RCC (equivalent to Stage IV RCC according to American Joint Committee on Cancer staging) renal cell carcinoma; Histologic confirmed clear cell renal cell carcinoma; No prior systemic therapy (interleukin-2, interferon-α, chemotherapy, bevacizumab, sunitinib, sorafenib, pazopanib, axitinib, everolimus or temsirolimus) for advanced or metastatic RCC; Measurable disease by RECIST; Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2; Adequate organ system functions; Patients must understand and be willing to sign the written informed consent form of this study. Exclusion Criteria: Non-clear cell renal cell carcinoma Pregnant or lactating female. History of another malignancy. Note: Subjects who have had another malignancy and have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin carcinoma or successfully treated in situ carcinoma are eligible. History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery) and meet all 3 of the following criteria are eligible: Are asymptomatic No evidence of active CNS metastases for ≥3 months prior to enrolment Have no requirement for steroids or anticonvulsants Clinically significant gastrointestinal abnormalities including, but not limited to: Malabsorption syndrome Major resection of the stomach or small bowel that could affect the absorption of study drug Active peptic ulcer disease Inflammatory bowel disease Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 28 days prior to beginning study treatment. History of any one or more of the following cardiovascular conditions within the past 12 months: Cardiac angioplasty or stenting Myocardial infarction Unstable angina Symptomatic peripheral vascular disease Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) History of cerebrovascular accident including transient ischemic attack (TIA). Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥150 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) of ≥ 90 mmHg

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1st Line Sunitinib and 2nd Line Axitinib<br>1st line sunitinib on a 4/2 schedule followed by axitinib 5 mg twice a day on 2nd line therapy | Drug: Sunitinib<br>* 1st line sunitinib on a 4/2 schedule followed by axitinib 5 mg twice a day on 2nd line therapy<br>* Other names: Axitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1st line Response Rate (RR) with Sunitinib in patients with VEGF pathway mutation | First Line Response Rate (RR) With Sunitinib (RECIST 1.1) in patients with VEGF pathway mutation | through study completion (up to 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1sr line RR with Sunitinib | First Line Response Rate (RR) with Sunitinib (RECIST 1.1) | through study completion (up to 2 years) | 
| 2nd Line RR with Axitinib | Second Line Response Rate (RR) with Axitinib (RECIST 1.1) | through study completion (up to 2 years) | 
| 1st line PFS with Sunitinib | First Line Progression Free Survival (PFS) with Sunitinib | through study completion (up to 2 years) | 
| 2nd PFS with Axitinib | Second Line Progression Free Survival (PFS) with Axitinib | through study completion (up to 2 years) | 
| Overall Survival (OS) | Overall Survival | through study completion (up to 2 years) | 
| Incidence of Treatment-Emergent Adverse Events | CTCAE v.4.0 | through study completion (up to 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarker, metastatic, sunitinib, axitinib, next generation sequencing, clear cell renal cell carcinoma