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

  Show 84 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

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

ClinicalTrials.gov processed this record on August 19, 2014