Safety and Efficacy of Bevacizumab Plus RAD001 Versus Interferon Alfa-2a and Bevacizumab in Adult Patients With Kidney Cancer (L2201)

This study has been completed.
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00719264
First received: July 15, 2008
Last updated: May 10, 2013
Last verified: May 2013
  Purpose

To estimate the difference in efficacy and safety of bevacizumab and RAD001 compared to bevacizumab and interferon alfa-2a for first-line treatment of patients with metastatic carcinoma of the kidney.


Condition Intervention Phase
Carcinoma, Renal Cell
Adenocarcinoma, Renal Cell
Nephroid Carcinoma
Carcinoma, Hypernephroid
Drug: bevacizumab, RAD001(Everolimus)
Drug: bevacizumab, interferon alfa-2a
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Multi-center Phase II Study to Compare Bevacizumab Plus RAD001 Versus Interferon Alfa-2a Plus Bevacizumab for the First-line Treatment of Patients With Metastatic Clear Cell Carcinoma of the Kidney

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression-free survival (PFS) of patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab based on an estimation of the chance of success of a possible subsequent phase III study [ Time Frame: Every 12 weeks until progressive disease as per independent central review or the initiation of a new secondary anti-cancer therapy until 200 PFS events are observed ] [ Designated as safety issue: No ]
    progression by central review, but anticancer treatment by clinical database (thru Case Report Form). Timeframe determined by central review.


Secondary Outcome Measures:
  • Overall survival (OS) treatment effect in patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab [ Time Frame: 2 years after the last patient randomized in the study ] [ Designated as safety issue: No ]
  • Objective response rate and response duration differences in patients who receive RAD001 plus bevacizumab versus patients who receive IFN plus bevacizumab [ Time Frame: when a total of 200 PFS events have been observed ] [ Designated as safety issue: No ]
    per independent central radiological review

  • Safety profile of RAD001 plus bevacizumab versus IFN plus bevacizumab [ Time Frame: until the last patient discontinued the study treatment + 28 days ] [ Designated as safety issue: Yes ]
  • Quality of life (QoL) of patients treated with RAD001 plus bevacizumab versus patients treated with IFN plus bevacizumab. [ Time Frame: when a total of 200 PFS events have been observed ] [ Designated as safety issue: No ]
    the timeframe is based on by the central review, however the actual QoL data is in the clinical database

  • Exposure of RAD001 in patients randomized to the treatment combination of RAD001 and bevacizumab [ Time Frame: until the last patient discontinued the study treatment + 28 days ] [ Designated as safety issue: No ]

Enrollment: 467
Study Start Date: November 2008
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: bevacizumab, RAD001 Drug: bevacizumab, RAD001(Everolimus)
Other Name: Afinitor
Active Comparator: bevacizumab, interferon alfa-2a
bevacizumab plus RAD001(Everolimus) versus bevacizumab and interferon alfa-2a
Drug: bevacizumab, interferon alfa-2a

  Eligibility

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

Inclusion Criteria:

  1. Patients with metastatic renal cell carcinoma
  2. Patients with at least one measurable lesion
  3. Patients with progressive metastatic renal cell carcinoma
  4. Patients who had a prior partial or complete nephrectomy
  5. Patients with a Karnofsky Performance Status ≥70%.
  6. Adequate bone marrow function
  7. Adequate liver function
  8. Adequate renal function
  9. Adequate coagulation profile

Exclusion Criteria:

  1. 4 weeks post-major surgery
  2. Patients who had radiation therapy within 28 days prior to start of study
  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 received prior therapy with VEGF pathway inhibitor
  8. Patients who have previously received systemic mTOR inhibitors
  9. Patients with a known hypersensitivity RAD001 (everolimus) or other rapamycins or to its excipients.
  10. Patients with history or current central nervous system (CNS) metastases or spinal cord compression.
  11. Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
  12. Patients with proteinuria at screening.
  13. Patients with inadequately controlled hypertension
  14. Patients receiving ongoing or with recent need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin
  15. Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent.
  16. Patients with a known history of HIV
  17. Patients with hypersensitivity to interferon alfa-2a or any component of the product.
  18. Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism
  19. Patients who have any severe and/or uncontrolled medical conditions or other conditions
  20. Left Ventricular Ejection Fraction < lower limit of institutional normal assessed by ECHO or MUGA
  21. Patients who have a history of another primary malignancy ≤ 3 years
  22. Female patients who are pregnant or breast feeding
  23. Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
  24. Patients unwilling to or unable to comply with the protocol

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00719264

  Show 106 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Roche Pharma AG
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00719264     History of Changes
Other Study ID Numbers: CRAD001L2201, 2008-000077-38
Study First Received: July 15, 2008
Last Updated: May 10, 2013
Health Authority: United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Ministry of Health
Czech Republic: State Institute for Drug Control
Egypt: Ministry of Health and Population
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Italy: Ministry of Health
Korea: Food and Drug Administration
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Taiwan: Department of Health
Thailand: Ministry of Public Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Renal cell carcinoma,
Adults,
Bevacizumab,
RAD001
Everolimus,
Interferon
Clear
Roferon
Avastin
Nephrectomy
newly diagnosed

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Interferon-alpha
Interferon Alfa-2a
Interferons
Everolimus
Sirolimus
Bevacizumab
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 15, 2014