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

Metastatic Renal Cell Carcinoma Clinical Trial

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02398552
• Other study ID #: BCH-RCC-150212
• Status: Recruiting
• Phase: Phase 2
• First received: March 20, 2015
• Last updated: February 27, 2016
• Start date: March 2015
• Est. completion date: March 2017

Study information

• Verified date: February 2016
• Source: Beijing Cancer Hospital
• Contact: Chuanliang Cui, MD
• Phone: 0086-10-88196951
• Email: 1008ccl[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: March 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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 ß-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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Metastatic Renal Cell Carcinoma

Intervention

Drug:
• Sunitinib
altenative schedules of sunitinib as first line therapy in metastatic renal cell carcinoma patients.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Chinese acadamy of medical science cancer institute & hospital	Beijing	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Sun Yat-sen university cancer center	Guangzhou	Guangdong
China	Cancer Hospital, Fudan University	Shanghai	Shanghai
China	Tianjin medical university cancer institute & hospital	Tianjin	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of adverse events		1 year	Yes
Primary	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	No
Secondary	The percentage of patients who can get complete response, partial response.		2 years	No