A Phase II Trila of Sunitinib Schedule 4/2 vs. Shedule 2/1 as First Line Therapy in Metastatic Renal Cell Carcinoma.

Study Overview
=================
Brief Summary
-----------------
Sunitinib given at 50 mg/day on schedule 4/2 (4 weeks on treatment, 2 weeks off) is the standard care for first-line treatment of metastatic renal cell carcinoma, but the schedule was reported with a high rate of dose reduction and dose discontinuation because of the safety profile. So investigators conducte this randomized, multi-center phase II study to determine whether a sunitinib regimen of 50 mg/day 2-weeks on/1-week off could provide the same efficacy in terms of progression-free survival, objective response, and overall survival, while reducing drug-related toxicity.

Detailed Description
-----------------
Sunitinib given at 50 mg/day on schedule 4/2 (4 weeks on treatment, 2 weeks off) is the standard care for first-line treatment of metastatic renal cell carcinoma, but the schedule was reported with a high rate of dose reduction and dose discontinuation because of the safety profile. Sunitinib 50mg/day on schedule 2/1 (2 weeks on treatment, 1 weeks off) was reported to be associated with significantly decrease toxicities in patients who initially experienced grade 3 or greater toxicity on the schedule 4/2 and could extend treatment duration considerably. Through this research, we would like to explore whether the schedule 2/1 of sunitinib 50 mg/day as first line therapy could provide the same efficacy as standard schedule 4/2 in terms of progression-free survival, objective response, and overall survival, while reducing drug-related toxicity in metastatic renal cell carcinoma patients.

Official Title
-----------------
A Randomized Phase II Trila of Sunitinib Four-weeks on/Two-weeks Off Versus Two-weeks on/One-week Off as First Line Therapy in Metastatic Renal Cell Carcinoma.

Conditions
-----------------
Metastatic Renal Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Sunitinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age≥18 years, ≤75 years, male or female Advanced renal cell carcinoma is diagnosed histologically or pathologically Treatment naive at diagnosed At least one measurable tumor lesion (Response Evaluation Criteria In Solid Tumors) Eastern Cooperative Oncology Group（ECOG) performance scale is 0 or 1 The expected life span is ≥12 weeks No contraindications for targeted therapy, with enough liver function and renal function and normal ECG recording Peripheral hemogram: neutrophil≥1.5×109/L, Plt≥100×109/L, Hgb≥90g/L Renal function: serum creatinine≤1.5 folds the upper limit of normal (ULN) For patients with non-metastatic liver dysfunction:alanine aminotransferase and aspartate aminotransferase≤2.5 ULN, For patients with metastatic liver dysfunction: alanine aminotransferase and aspartate aminotransferase≤5 ULN The patients participate voluntarily and have signed the informed consent form Exclusion Criteria: Patients who have received any systemic therapy including targeted therapy,immunotherapy,chemotherapy etc at diagnosed. Pregnant and lactating women, or female patients of child-bearing age without taking contraceptive measures Patients with severe acute infection without being controlled effectively or having pyogenic and chronic infections with persistently unhealed wounds Past history of serious heart diseases, including: cardiac function classification ≥NYHA class II, unstable angina pectoris, myocardial infarction, arrhythmia requiring anti-arrhythmic drug therapy (excluding β-blockers or digoxin), and uncontrolled hypertension Patients with a history of HIV infection or active phase of chronic hepatitis B/C negative imaging examination result 4 weeks prior to enrollment) Epilepsy patients requiring drug therapy (e.g. steroids or antiepileptic drugs) A history of allogeneic organ transplantation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sunitinib 50mg/day schedule 4/2<br>Sunitinib 50mg/day 4 weeks on/2 weeks off per 6 weeks till disease progression or intolerable toxicity. | Drug: Sunitinib<br>* altenative schedules of sunitinib as first line therapy in metastatic renal cell carcinoma patients.<br>* Other names: Sutent;|
| Experimental: Sunitinib 50mg/day schedule 2/1<br>Sunitinib 50mg/day 2 weeks on/1 week off per 6 weeks till disease progression or intolerable toxicity. | Drug: Sunitinib<br>* altenative schedules of sunitinib as first line therapy in metastatic renal cell carcinoma patients.<br>* Other names: Sutent;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress-free survival (PFS) | Time from enrollment to the dates of disease progression,death from any cause or last tumor assessment reported between date of first patient enrollment until March 2017 cut off date | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients who can get complete response, partial response. |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
metastatic renal cell carcinoma, sunitinib, schedule 2weeks on/1 week off