Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma

Renal Cell Carcinoma Clinical Trial

— RECORD-3  

Official title:

An Open-label, Multicenter Phase II Study to Compare the Efficacy and Safety of RAD001 as First-line Followed by Second-line Sunitinib Versus Sunitinib as First-line Followed by Second-line RAD001 in the Treatment of Patients With Metastatic Renal Cell Carcinoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00903175
• Other study ID #: CRAD001L2202
• Secondary ID: 2009-011056-21
• Status: Completed
• Phase: Phase 2
• First received: April 24, 2009
• Last updated: August 6, 2015
• Start date: October 2009
• Est. completion date: May 2015

Study information

• Verified date: August 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBrazil: Ministry of HealthCanada: Health CanadaBelgium: Federal Agency for Medicinal Products and Health ProductsDenmark: Danish Medicines AgencyFrance: Ministry of HealthGermany: Ministry of HealthItaly: Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Spain: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

This study will assess the efficacy and safety of first-line RAD001 followed by second-line sunitinib versus the opposite sequence: first-line sunitinib followed by second-line RAD001 for the treatment of patients with MRCC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 471
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients with advanced renal cell carcinoma.

2. Patients with at least one measurable lesion.

3. Patients with a Karnofsky Performance Status =70%.

4. Adequate bone marrow function.

5. Adequate liver function.

6. Adequate renal function.

7. Left ventricular ejection fraction (LVEF) = lower limit of institutional normal (LLN)

8. Women of childbearing potential must have had a negative serum pregnancy test within 14 days prior to the administration of the study medication. Adequate contraception must be used while on study.

Exclusion Criteria:

1. Less than 4 weeks post-major surgery

2. Patients who had radiation therapy within 4 weeks prior to start of study treatment (palliative radiotherapy to bone lesions allowed within 2 weeks prior to study treatment start).

3. Patients in need for major surgical procedure during the course of the study

4. Patients with a serious non-healing wound, ulcer, or bone fracture

5. Patients with a history of seizure(s) not controlled with standard medical therapy

6. Patients who have received prior systemic treatment for their metastatic RCC

7. Patients who have previously received systemic mTOR inhibitors (sirolimus, temsirolimus, everolimus) or VEGF inhibitors. Note: History of adjuvant immunotherapy, vaccines or adjuvant sorafenib following localized surgical nephrectomy is acceptable.

8. Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins or to its excipients

9. Patients with a known hypersensitivity to sunitinib or its excipients

10. Untreated central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery plus or minus radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible:

• Are asymptomatic and,

• have had no evidence of active CNS metastases for = 6 months prior to enrollment and,

• have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC)

11. 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 intra abdominal abscess within 28 days prior to beginning study treatment.

12. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of =150mmHg or diastolic blood pressure (DBP) of = 90mmHg]

13. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent

14. Patients with a known history of HIV seropositivity.

15. Patients with active bleeding.

16. Patients who have any severe and/or uncontrolled medical conditions or other conditions within the past 12 months that could affect their participation in the study such as:

• Cardiac angioplasty or stenting, unstable angina pectoris, symptomatic peripheral vascular disease, symptomatic congestive heart failure (NYHA II, III, IV), myocardial infarction = 6 months prior to first study treatment, serious uncontrolled cardiac arrhythmia, cerebrovascular accidents = 6 months before study treatment start.

• Prolongation of corrected QT interval (QTc) > 500 milliseconds (msecs).

• Severally impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air.

• Poorly controlled diabetes as defined by fasting serum glucose >2.0 x ULN.

• Any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study.

• Liver disease such as chronic active hepatitis or chronic persistent hepatitis.

17. History of cerebrovascular accident (CVA) including transient ischemic attack (TIA).

18. History of pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible.

19. Patients who have a history of another primary malignancy and off treatment for = 3 years

20. Female patients of child-bearing potential who are not using adequate birth control methods, or who are pregnant or breast feeding.

21. Patients who are using other investigational agents or who had received investigational drugs = 2 weeks prior to study treatment start.

22. Patients unwilling or unable to comply with the protocol.

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• RAD001

• sunitinib

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Australia	Novartis Investigative Site	Woodville	South Australia
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Sao Paulo	SP
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Saskatoon	Saskatchewan
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoria	British Columbia
Denmark	Novartis Investigative Site	Herlev
France	Novartis Investigative Site	Angers cedex 9
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Paris
France	Novartis Investigative Site	Vandoeuvre-Les-Nancy Cede
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Weiden
Hong Kong	Novartis Investigative Site	Hongkong
Hong Kong	Novartis Investigative Site	Shatin, New Territories
Italy	Novartis Investigative Site	Arezzo	AR
Italy	Novartis Investigative Site	Modena	MO
Italy	Novartis Investigative Site	Napoli
Korea, Republic of	Novartis Investigative Site	Daejeon
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Mexico	Novartis Investigative Site	Chihuahua
Netherlands	Novartis Investigative Site	Den Haag
Netherlands	Novartis Investigative Site	Maastricht
Peru	Novartis Investigative Site	Jesus Maria	Lima
Spain	Novartis Investigative Site	Elche	Alicante
Spain	Novartis Investigative Site	Lleida	Cataluna
Spain	Novartis Investigative Site	Sabadell	Barcelona
Spain	Novartis Investigative Site	Sevilla	Andalucia
Taiwan	Novartis Investigative Site	Niaosong Township
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Thailand	Novartis Investigative Site	Bangkok
Turkey	Novartis Investigative Site	Istanbul
United Kingdom	Novartis Investigative Site	Bristol	Avon
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Nottingham
United States	University Cancer & Blood Center, LLC Dept of NE GCC (2)	Athens	Georgia
United States	Georgia Health Sciences University Dept. of MCG	Augusta	Georgia
United States	University of Colorado Dept. of Anschutz Cancer (2)	Aurora	Colorado
United States	VA Maryland Health Care Dept.of GreenbaumCancerCent(7)	Baltimore	Maryland
United States	Weinberg Cancer Institute at Franklin Square Hospital	Baltimore	Maryland
United States	St. Luke's Hospital and Health Network St Luke's Hospital (2)	Bethlehem	Pennsylvania
United States	Billings Clinic Dept of Billings Clinic(2)	Billings	Montana
United States	University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)	Birmingham	Alabama
United States	Lynn Cancer Institute	Boca Raton	Florida
United States	University of North Carolina Dept. of LinbergerCancerCtr(3)	Chapel Hill	North Carolina
United States	Levine Cancer Institute Oncology	Charlotte	North Carolina
United States	NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital	Chicago	Illinois
United States	Duke University Medical Center Duke	Durham	North Carolina
United States	Highlands Oncology Group HighlandsOncGrp-Bentonville(2)	Fayetteville	Arkansas
United States	The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)	Fort Worth	Texas
United States	Hackensack University Medical Center DeptofHackensackUniv.MedCtr.	Hackensack	New Jersey
United States	University of California San Diego - Moores Cancer Center Dept of Moores Cancer Ctr (5)	La Jolla	California
United States	Clinical Research Alliance	Lake Success	New York
United States	University of California at Los Angeles Dept. of UCLA (3)	Los Angeles	California
United States	Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)	Maywood	Illinois
United States	The West Clinic Dept. of the West Clinic	Memphis	Tennessee
United States	Crescent City Research Consortium, LLC SC	Metairie	Louisiana
United States	University of Miami SC	Miami	Florida
United States	Aurora Advanced Healthcare SC	Milwaukee	Wisconsin
United States	University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.	Mobile	Alabama
United States	Norwalk Hospital Norwlak SC	Norwalk	Connecticut
United States	Memorial Sloan Kettering Cancer Center Dept. of MSKCC	NY	New York
United States	University of Oklahoma Health Sciences Center Dept of OHSC	Oklahoma City	Oklahoma
United States	MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando	Orlando	Florida
United States	Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)	Salt Lake City	Utah
United States	Summit Cancer Care	Savannah	Georgia
United States	SUNY - Upstate Medical University Div. of Hematology-Oncology	Syracuse	New York
United States	East Texas Medical Center Cancer Institute	Tyler	Texas
United States	Cooper Cancer Center	Voorhees	New Jersey
United States	Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Denmark,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess if Progression Free Survival (PFS) after first-line of treatment in patients who receive RAD001 will be non-inferior to the PFS of patients who receive sunitinib after first-line treatment.		6 - 12 months	No
Secondary	To compare the second Progression Free Survival (PFS) after the second-line of treatment in patients who receive RAD001 followed by sunitinib versus the second PFS after the second-line of treatment in patients who receive sunitinib followed by RAD001.		6 - 9 months	No
Secondary	To compare the safety profile of RAD001 versus sunitinib as first-line and overall for both the first-line and second-line.		6 - 16 months	Yes
Secondary	To assess the patient reported outcomes (PRO) in disease related symptoms and overall quality of life during each line of treatment.		6 - 16 months	No
Secondary	To estimate the objective response rate and duration of response differences during each line of treatment.		6 - 16 months	No
Secondary	To compare the overall survival rates during each line of treatment.		6 - 36 months	No

External Links

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