Efficacy and Safety Comparison of RAD001 Versus Sunitinib in the First-line and Second-line Treatment of Patients With Metastatic Renal Cell Carcinoma (RECORD-3)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00903175
First received: April 24, 2009
Last updated: April 21, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Renal Cell Carcinoma
Drug: RAD001
Drug: sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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. [ Time Frame: 6 - 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Time Frame: 6 - 9 months ] [ Designated as safety issue: No ]
  • To compare the safety profile of RAD001 versus sunitinib as first-line and overall for both the first-line and second-line. [ Time Frame: 6 - 16 months ] [ Designated as safety issue: Yes ]
  • To assess the patient reported outcomes (PRO) in disease related symptoms and overall quality of life during each line of treatment. [ Time Frame: 6 - 16 months ] [ Designated as safety issue: No ]
  • To estimate the objective response rate and duration of response differences during each line of treatment. [ Time Frame: 6 - 16 months ] [ Designated as safety issue: No ]
  • To compare the overall survival rates during each line of treatment. [ Time Frame: 6 - 36 months ] [ Designated as safety issue: No ]

Enrollment: 470
Study Start Date: October 2009
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: everolimus, sunitinib Drug: RAD001
Active Comparator: sunitinib, everolimus Drug: sunitinib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00903175

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham/ Kirklin Clinic Comprehensive CancerCenter (1)
Birmingham, Alabama, United States, 35294-0006
University of South Alabama / Mitchell Cancer Institute Dept. of Mitchell Cancer Inst.
Mobile, Alabama, United States, 36688
United States, Arkansas
Highlands Oncology Group HighlandsOncGrp-Bentonville(2)
Fayetteville, Arkansas, United States, 72703
United States, California
University of California San Diego Dept of Moores Cancer Ctr (5)
La Jolla, California, United States, 92093-0658
University of California at Los Angeles Dept. of UCLA (3)
Los Angeles, California, United States, 90095
United States, Colorado
University of Colorado Dept. of Anschutz Cancer (2)
Aurora, Colorado, United States, 80045
United States, Connecticut
Norwalk Hospital Norwlak SC
Norwalk, Connecticut, United States, 06856
United States, District of Columbia
Georgetown University/Lombardi Cancer Center Dept.of Lombardi Cancer Ctr (2
Washington, District of Columbia, United States, 20007-2197
United States, Florida
Lynn Cancer Institute
Boca Raton, Florida, United States, 33486
University of Miami SC
Miami, Florida, United States, 33136
MD Anderson Cancer Center - Orlando Dept.ofMDACC-Orlando
Orlando, Florida, United States, 32806
United States, Georgia
University Cancer & Blood Center, LLC Dept of NE GCC (2)
Athens, Georgia, United States, 30607
Georgia Health Sciences University Dept. of MCG
Augusta, Georgia, United States, 30912
Summit Cancer Care
Savannah, Georgia, United States, 31405
United States, Illinois
NorthwesternUniv.Med.School/Robert H. Lurie Comp.Cancer Ctr Dept.ofNorthwesternMemHospital
Chicago, Illinois, United States, 60611
Loyola University Medical Center /Cardinal Bernardin Cancer Cardinal Bernardin Cancer (3)
Maywood, Illinois, United States, 60153
United States, Louisiana
Crescent City Research Consortium, LLC SC
Metairie, Louisiana, United States, 70006
United States, Maryland
Weinberg Cancer Institute at Franklin Square Hospital
Baltimore, Maryland, United States, 21237-3998
VA Maryland Health Care Dept.of GreenbaumCancerCent(7)
Baltimore, Maryland, United States, 21201
United States, Montana
Billings Clinic Dept of Billings Clinic(2)
Billings, Montana, United States, 59107
United States, New Jersey
Hackensack University Medical Center DeptofHackensackUniv.MedCtr.
Hackensack, New Jersey, United States, 07601
Cooper Cancer Center
Voorhees, New Jersey, United States, 08043
United States, New York
NYU Langone Arena Oncology
Lake Success, New York, United States, 11042
Memorial Sloan Kettering Cancer Center Dept. of MSKCC
New York, New York, United States, 10021
SUNY - Upstate Medical University Div. of Hematology-Oncology
Syracuse, New York, United States, 13210
United States, North Carolina
University of North Carolina Dept. of LinbergerCancerCtr(3)
Chapel Hill, North Carolina, United States, 27599-7295
Levine Cancer Institute Oncology
Charlotte, North Carolina, United States, 28203
Duke University Medical Center Duke
Durham, North Carolina, United States, 27710
United States, Oklahoma
University of Oklahoma Health Sciences Center Dept of OHSC
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
St. Luke's Hospital and Health Network St Luke's Hospital (2)
Bethlehem, Pennsylvania, United States
United States, Tennessee
The West Clinic Dept. of the West Clinic
Memphis, Tennessee, United States, 38120
United States, Texas
The Center for Cancer and Blood Disorders Dept. of The Ctr for C & BD(2)
Fort Worth, Texas, United States, 76104
East Texas Medical Center Cancer Institute
Tyler, Texas, United States, 75701
United States, Utah
Utah Cancer Specialists Dept.of Utah Cancer Spec. (3)
Salt Lake City, Utah, United States, 84106
United States, Wisconsin
Aurora Advanced Healthcare SC
Milwaukee, Wisconsin, United States, 53215
Argentina
Novartis Investigative Site
La Plata, Buenos Aires, Argentina, B1902CMK
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Rosario, Santa Fe, Argentina, S2002KDS
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Buenos Aires, Argentina, C1405BCH
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Tucuman, Argentina, T4000IAK
Australia, South Australia
Novartis Investigative Site
Woodville, South Australia, Australia, 5011
Brazil
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Rio de Janeiro, RJ, Brazil, 20230-130
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Porto Alegre, RS, Brazil, 90610-000
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São Paulo, SP, Brazil, 05403-000
Canada, Alberta
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Calgary, Alberta, Canada, T2N 4N2
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Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
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Victoria, British Columbia, Canada, V8R 6V5
Canada, Ontario
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Toronto, Ontario, Canada, M4N 3M5
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Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
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Greenfield Park, Quebec, Canada, J4V 2H1
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Montreal, Quebec, Canada, H2X 3J4
Canada, Saskatchewan
Novartis Investigative Site
Saskatoon, Saskatchewan, Canada, S7N 4H4
Denmark
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Herlev, Denmark, DK-2730
France
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Angers cedex 9, France, 49033
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Lille Cedex, France, 59020
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Paris, France, 75015
Novartis Investigative Site
Vandoeuvre-Les-Nancy Cede, France, 54511
Germany
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Aschaffenburg, Germany, 63739
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Berlin, Germany, 10098
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Weiden, Germany, 92637
Hong Kong
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Hongkong, Hong Kong
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Shatin, New Territories, Hong Kong
Italy
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Arezzo, AR, Italy, 52100
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Modena, MO, Italy, 41100
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Napoli, Italy, 80132
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 120-752
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Seoul, Korea, Korea, Republic of, 110 744
Novartis Investigative Site
Daejeon, Korea, Republic of, 301-747
Novartis Investigative Site
Seoul, Korea, Republic of, 738-736
Mexico
Novartis Investigative Site
Chihuahua, Mexico, 31000
Netherlands
Novartis Investigative Site
Den Haag, Netherlands, 2545 CH
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Maastricht, Netherlands, 6229 HX
Peru
Novartis Investigative Site
Jesus Maria, Lima, Peru, 11
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Sabadell, Barcelona, Spain, 08208
Novartis Investigative Site
Lleida, Cataluña, Spain, 25198
Novartis Investigative Site
Elche, Murcia, Spain, 03202
Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 112
Novartis Investigative Site
Niaosong Township, Taiwan, 83301
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10700
Turkey
Novartis Investigative Site
Istanbul, Turkey, 34093
United Kingdom
Novartis Investigative Site
Bristol, Avon, United Kingdom, BS2 8ED
Novartis Investigative Site
London, United Kingdom, SW3 6JJ
Novartis Investigative Site
Nottingham, United Kingdom, NG5 1PB
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00903175     History of Changes
Other Study ID Numbers: CRAD001L2202, 2009-011056-21
Study First Received: April 24, 2009
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration
Brazil: Ministry of Health
Canada: Health Canada
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
France: Ministry of Health
Germany: Ministry of Health
Italy: Ministry of Health
Netherlands: Medicines Evaluation Board (MEB)
Spain: Ministry of Health

Keywords provided by Novartis:
RAD001
everolimus
Afinitor®
Sutent®
sunitinib
renal cell carcinoma
kidney cancer
metastatic renal cell cancer
advanced kidney cancer

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Adenocarcinoma
Kidney Diseases
Kidney Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms
Everolimus
Sirolimus
Sunitinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014