Clinical trial NCT02398552: A Phase II Trila of Sunitinib Schedule 4/2 vs. Shedule 2/1 as First Line Therapy in Metastatic Renal Cell Carcinoma.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Renal Cell Carcinoma
Keywords: metastatic renal cell carcinoma
sunitinib
schedule 2weeks on/1 week off
Lead sponsor: Peking University Cancer Hospital & Institute
Sponsor class: OTHER
First posted: 2015-03-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: progress-free survival (PFS)
timeFrame: 2 years
Secondary outcomes:
measure: The percentage of patients who can get complete response, partial response.
timeFrame: 2 years
Other outcomes:
measure: Number of adverse events
timeFrame: 1 year
Locations:
city: Beijing
country: China
facility: Chinese acadamy of medical science cancer institute & hospital
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen university cancer center
state: Guangdong
city: Shanghai
country: China
facility: Cancer Hospital, Fudan University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin medical university cancer institute & hospital
state: Tianjin
Study officials:
affiliation: Peking University Cancer Hospital & Institute
name: Jun Guo, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, Negrier S, Szczylik C, Pili R, Bjarnason GA, Garcia-del-Muro X, Sosman JA, Solska E, Wilding G, Thompson JA, Kim ST, Chen I, Huang X, Figlin RA. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009 Aug 1;27(22):3584-90. doi: 10.1200/JCO.2008.20.1293. Epub 2009 Jun 1.
citation: Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ. Relationship between exposure to sunitinib and efficacy and tolerability endpoints in patients with cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer Chemother Pharmacol. 2010 Jul;66(2):357-71. doi: 10.1007/s00280-009-1170-y. Epub 2009 Dec 5.
citation: Neri B, Vannini A, Brugia M, Muto A, Rangan S, Rediti M, Tassi R, Cerullo C. Biweekly sunitinib regimen reduces toxicity and retains efficacy in metastatic renal cell carcinoma: a single-center experience with 31 patients. Int J Urol. 2013 May;20(5):478-83. doi: 10.1111/j.1442-2042.2012.03204.x. Epub 2012 Nov 1.