Safety and Efficacy of Bevacizumab Plus RAD001 Versus Interferon Alfa-2a and Bevacizumab for the First-line Treatment in Adult Patients With Kidney Cancer

NCT ID: NCT00719264

Last Updated: 2017-03-20

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

365 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-12

Study Completion Date

2013-04-15

Brief Summary

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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.

Detailed Description

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Conditions

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Carcinoma Adenocarcinoma Renal Cell Nephroid Carcinoma Hypernephroid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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bevacizumab, RAD001 (everolimus)

Participants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks

Group Type EXPERIMENTAL

RAD001(everolimus)

Intervention Type DRUG

10 mg qd

bevacizumab

Intervention Type DRUG

10 mg/kg every 2 weeks

bevacizumab, interferon alfa-2a (IFN)

Participants received subcutaneous IFN dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3 of treatment and subsequently (if tolerated), 3 times per week plus intravenous bevacizumab 10 mg/kg every 2 weeks

Group Type ACTIVE_COMPARATOR

interferon alfa-2a

Intervention Type DRUG

dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3

bevacizumab

Intervention Type DRUG

10 mg/kg every 2 weeks

Interventions

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RAD001(everolimus)

10 mg qd

Intervention Type DRUG

interferon alfa-2a

dose escalated from 3 MIU (million international unit) during week 1, 6 MIU during week 2, and 9 MIU during week 3

Intervention Type DRUG

bevacizumab

10 mg/kg every 2 weeks

Intervention Type DRUG

Other Intervention Names

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Afinitor

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Roche Pharma AG

INDUSTRY

Sponsor Role collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, United States

Site Status

City of Hope National Medical Center Dept.ofCityofHopeMedicalCtr(3)

Duarte, California, United States

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USC/Kenneth Norris Comprehensive Cancer Center Regulatory Contact 3

Los Angeles, California, United States

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University of California at Los Angeles Dept. of Hem/Oncology

Los Angeles, California, United States

Site Status

Karmanos Cancer Institute Dept.of KarmanosCancerInst (5)

Detroit, Michigan, United States

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Nevada Cancer Institute Dept. of Nevada Cancer (3)

Las Vegas, Nevada, United States

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St. Luke's Hospital and Health Network St. Luke's Cancer Network

Bethlehem, Pennsylvania, United States

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Las Colinas Hematology Oncology Grapevine

Irving, Texas, United States

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Seattle Cancer Care Alliance Dept. of SCCA

Seattle, Washington, United States

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Novartis Investigative Site

Brussels, , Belgium

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Brussels, , Belgium

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Charleroi, , Belgium

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Kortrijk, , Belgium

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Leuven, , Belgium

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Liège, , Belgium

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Rio de Janeiro, Rio de Janeiro, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Porto Alegre, Rio Grande do Sul, Brazil

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Ribeirão Preto, São Paulo, Brazil

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Santo André, São Paulo, Brazil

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São Paulo, São Paulo, Brazil

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Olomouc, , Czechia

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Prague, , Czechia

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Cairo, Egypt, Egypt

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Cairo, , Egypt

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Strasbourg, Cedex, France

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Suresnes, France, France

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Avignon, , France

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Bordeaux, , France

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Caen, , France

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La Roche-sur-Yon, , France

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Montellier Cedex 5, , France

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Nantes, , France

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Reims, , France

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Rouen, , France

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Strasbourg, , France

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Toulouse, , France

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Berlin, , Germany

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Berlin, , Germany

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Dessau, , Germany

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Essen, , Germany

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Frankfurt, , Germany

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Frankfurt, , Germany

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Göttingen, , Germany

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Hamburg, , Germany

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Hanover, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Tübingen, , Germany

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Shatin, New Territories, Hong Kong, Hong Kong

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Tuenmen, Hong Kong, Hong Kong

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Budapest, , Hungary

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Brescia, BS, Italy

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Cremona, CR, Italy

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Catanzaro, CZ, Italy

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Florence, FI, Italy

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Milan, MI, Italy

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Modena, MO, Italy

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Perugia, PG, Italy

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Aviano, PN, Italy

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Pavia, PV, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Trento, TN, Italy

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Negrar, VR, Italy

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Napoli, , Italy

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Leiden, Netherlands, Netherlands

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Moscow, Moscow, Russia

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Obninsk, Russia, Russia

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Pretoria, , South Africa

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Pretoria, , South Africa

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Goyang-si, Gyeonggi-do, South Korea

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Seoul, Korea, South Korea

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Daegu, , South Korea

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Seoul, , South Korea

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Taegu, , South Korea

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Jaén, Andalusia, Spain

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Barcelona, Barcelona, Spain

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Santander, Cantabria, Spain

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Madrid, Madrid, Spain

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Madrid, Madrid, Spain

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Zaragoza, Zaragoza, Spain

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Santander, , Spain

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Bern, Switzerland, Switzerland

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Chur, , Switzerland

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Taichung, Taiwan, Taiwan

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Taipei, Taiwan, Taiwan

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Taipei, Taiwan, Taiwan

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Taipei, Taiwan, ROC, Taiwan

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Linkou District, , Taiwan

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Bangkok, , Thailand

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Songkhla, , Thailand

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Adana, Turkey, Turkey (Türkiye)

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Ankara, Turkey, Turkey (Türkiye)

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Bursa, Turkey, Turkey (Türkiye)

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Altunizade, , Turkey (Türkiye)

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Antalya, , Turkey (Türkiye)

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Balcova / Izmir, , Turkey (Türkiye)

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Mecidiyekoy/Istanbul, , Turkey (Türkiye)

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Northwood, Middlesex, United Kingdom

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Glasgow, , United Kingdom

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Southampton, , United Kingdom

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Countries

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United States Belgium Brazil Czechia Egypt France Germany Hong Kong Hungary Italy Netherlands Russia Singapore South Africa South Korea Spain Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom

References

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Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

Reference Type DERIVED
PMID: 37146227 (View on PubMed)

Ravaud A, Barrios CH, Alekseev B, Tay MH, Agarwala SS, Yalcin S, Lin CC, Roman L, Shkolnik M, Anak O, Gogov S, Pelov D, Louveau AL, Melichar B. RECORD-2: phase II randomized study of everolimus and bevacizumab versus interferon alpha-2a and bevacizumab as first-line therapy in patients with metastatic renal cell carcinoma. Ann Oncol. 2015 Jul;26(7):1378-84. doi: 10.1093/annonc/mdv170. Epub 2015 Apr 7.

Reference Type DERIVED
PMID: 25851632 (View on PubMed)

Related Links

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http://www.novartisclinicaltrials.com/webapp/etrials/searchTrial.do?t=i&trialID=688

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Other Identifiers

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2008-000077-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRAD001L2201

Identifier Type: -

Identifier Source: org_study_id

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