Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)

Study Overview
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Brief Summary
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Evaluation of unfavourable outcome-related factors in patients affected by renal cell cancer in treatment with everolimus and previously treated with a Vascular endothelial growth factor (VEGF) inhibitor (i.e. sunitinib, sorafenib,pazopanib, or bevacizumab+interferon)

Detailed Description
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Predictive factors to be considered are: histology, Heng risk group, Eastern Cooperative Oncology Group-performance status (ECOG-PS), site of metastases, glycemia and cholesterolemia. The data collected in this real life population could contribute to identify clinical factors that predict favourable outcomes in patients treated with everolimus after failure or a a first-line treatment with a VEGF inhibitor.

Official Title
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Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus After Failure of a First-line Treatment With VEGF Inhibitor

Conditions
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Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 years or older, with histologically or cytologically confirmed mRCC (clear cell or not clear cell); ECOG-PS 0-1-2; With target and/or non-target lesions according to Response Evaluation Criteria In Solid Tumours (RECIST) 1.1; Following failure of a previous treatment with VEGF-targeted therapy (e.g. sunitinib, sorafenib, pazopanib, or bevacizumab+interferon); For whom a decision has been taken to initiate everolimus treatment or patient currently receiving treatment with everolimus by a period of time ≤30 days; Willing and able to comply with follow-up and all other protocol requirements and able to commence treatment within 21 days; Written informed consent obtained before any screening procedure and according to local guidelines. Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: Previous treatment with everolimus or at the date of written informed consent provision receiving everolimus by more than 30 days; Symptomatic central nervous system metastases. Patients may be eligible if the central nervous system metastases have been adequately treated (surgery or radiotherapy), and do not require ongoing corticosteroids for control of symptoms and have had no evidence of progression for at least three months; Other malignancy diagnosed within the last 5 years, except the following, if adequately treated: superficial squamous cell carcinoma or basal cell carcinoma of skin, superficial bladder cancer (T1 and G1 or T1 and G2), stage 1 cervical cancer; Treatment with an investigational agent in the past 4 weeks; Clinically relevant human immunodeficiency virus, hepatitis B virus, hepatitis C virus infection; Non adequate liver function as shown by: serum or plasma ALT and AST >3.0x upper limit of normal (ULN) >5 if hepatic metastases are present; Serum or plasma total bilirubin: >1.5xULN (excepted for patients with Gilbert's syndrome); Non adequate renal function as shown by serum creatinine >2.5xULN; Any of the following in the last year: myocardial infarction, severe/ unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack or pulmonary embolism; Ongoing grade ≥2 cardiac dysrhythmias, atrial fibrillation of any grade or prolongation of the corrected QT interval to >450 msec for males or >470 msec for females; Pregnancy (negative pregnancy test required for women of child-bearing potential), breast feeding; Inadequate contraception. Women must be post-menopausal, surgically sterile, or use a reliable form of contraception. Men must be surgically sterile or use a barrier method of contraception; Known allergy or hypersensitivity to everolimus or its excipients.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Everolimus<br>All patients will receive everolimus 10 mg orally per day. Treatment will continue until progression, unacceptable toxicity, patient refusal or medical decision | Drug: Everolimus<br>* Patients will start study treatment on day 1 and will be treated with daily doses of everolimus (10 mg daily tablets).<br>* Other names: Afinitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| predictive factors identification | To identify factors predictive of a favourable outcome, in terms of survival free from an unfavourable event, in patients treated with everolimus as second line treatment for metastatic renal cell carcinoma (mRCC). A favourable outcome is being alive and on treatment without both disease progression (according to RECIST 1.1) and HRQoL deterioration (7-point decrease from baseline evaluation on the EQ-5D VAS). | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) of everolimus as second line treatment | PFS distributions will be estimated using the Kaplan-Meier method and compared using the log-rank test. | 36 months | 
| health related quality of life (HRQoL) | As measured by EQ-5D questionnaire. It will be described at each time by using summary statistical measures for continuous variables | 36 months | 
| drug-related toxicity | assessed by the National Cancer Institute-Common Terminology Criteria for adverse events (NCI-CTCAE), version 4.03. The frequency of maximum toxicity grade experienced by each patient for each specific toxicity will be presented as well as the frequency of patients experiencing grade 3 or 4 (grade 2 for neurotoxicity) events, and SADRs. | 36 months | 
| compliance | Treatment compliance will be assessed by evaluating the dose intensity (total dose divided by duration of exposure to treatment in weeks), and calculating the frequencies and proportion of patients who modified or interrupted the treatment. | 36 months |