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

NCT00719264 | Completed Phase 2 Results

• 2 other identifiers: CRAD001L22012008-000077-38
• Study Type: interventional
• Target: 365
• Locations: 21 countries
• Sites: 109

Brief Summary

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.

Conditions

Carcinoma; Adenocarcinoma; Renal Cell; Nephroid Carcinoma; Hypernephroid

Keywords

Renal cell carcinoma; Adults; Bevacizumab; RAD001; Everolimus; Interferon; Clear; Roferon; Avastin; Nephrectomy; newly diagnosed

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab

  Tumor response and disease progression were assessed using response evaluation criteria in solid tumors (RECIST), version 1.0. All target and non-target lesions identified at baseline were assessed using the same method, CT scan with contrast or MRI with contrast, throughout the trial. All scans were reviewed by independent, central radiology. Disease progression was defined as: 1) a 20% increase in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameters of all target lesions recorded at or after baseline or 2) the appearance of a new lesions or 3) the unequivocal progression of non-target lesions overall.

  Time from randomization to the date of radiological progressive disease as per independent central review, death from any cause, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cutoff date.

Secondary Outcomes (7)

• Overall Survival (OS) Treatment Effect in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab

  Time from randomization to the date of death from any cause, reported between date of first participant randomized and up to 2 years after the last participant randomized (data cutoff: 30Aug2012)

• Best Overall Response in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab

  Time from first participant randomized until 31Dec2011, cutoff date.

• Response Duration Differences in Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab

  Time from first documented response date of radiological progressive disease as per independent central review, death due to underlying cancer, or last tumor assessment, reported between date of first participant randomized until 31Dec2011, cut-off date.

• Number of Participants Who Experienced Adverse Events (AEs), Serious Adverse Events and Deaths

  From the first participant randomized until the last patient discontinued the study treatment + 28 days

• Time to Definitive Deterioration of the Functional Assessment of Cancer Therapy Kidney Symptom Index, Disease Related Symptoms (FKSI-DRS) Risk Score by at Least 2 Score Units

  Time from randomization to the date of definitive deterioration (defined as no later increase above the threshold observed during the study), or date of last assessment, reported between date of first patient randomized until 31Dec2011

Study Arms (2)

bevacizumab, RAD001 (everolimus)

EXPERIMENTAL

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

Drug: RAD001(everolimus); Drug: bevacizumab

bevacizumab, interferon alfa-2a (IFN)

ACTIVE COMPARATOR

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

Drug: interferon alfa-2a; Drug: bevacizumab

Interventions

RAD001(everolimus) DRUG

10 mg qd

Also known as: Afinitor

bevacizumab, RAD001 (everolimus)

interferon alfa-2a DRUG

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

bevacizumab, interferon alfa-2a (IFN)

bevacizumab DRUG

10 mg/kg every 2 weeks

bevacizumab, RAD001 (everolimus); bevacizumab, interferon alfa-2a (IFN)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with metastatic renal cell carcinoma
• Patients with at least one measurable lesion
• Patients with progressive metastatic renal cell carcinoma
• Patients who had a prior partial or complete nephrectomy
• Patients with a Karnofsky Performance Status ≥70%.
• Adequate bone marrow function
• Adequate liver function
• Adequate renal function
• Adequate coagulation profile

You may not qualify if:

• weeks post-major surgery
• Patients who had radiation therapy within 28 days prior to start of study
• Patients in need for major surgical procedure during the course of the study.
• Patients with a serious non-healing wound, ulcer, or bone fracture.
• Patients with a history of seizure(s) not controlled with standard medical therapy.
• Patients who have received prior systemic treatment for their metastatic RCC.
• Patients who received prior therapy with VEGF pathway inhibitor
• Patients who have previously received systemic mTOR inhibitors
• Patients with a known hypersensitivity RAD001 (everolimus) or other rapamycins or to its excipients.
• Patients with history or current central nervous system (CNS) metastases or spinal cord compression.
• Patients with a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
• Patients with proteinuria at screening.
• Patients with inadequately controlled hypertension
• Patients receiving ongoing or with recent need for full therapeutic dose of oral or parenteral anticoagulants or chronic daily treatment with aspirin
• Patients receiving chronic systemic treatment with corticosteroids or another immunosuppressive agent.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Roche Pharma AG: collaborator

Study Sites (109)

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

Location

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

Duarte, California, 91010-3000, United States

Location

USC/Kenneth Norris Comprehensive Cancer Center Regulatory Contact 3

Los Angeles, California, 90053, United States

Location

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

Los Angeles, California, 90095, United States

Location

Karmanos Cancer Institute Dept.of KarmanosCancerInst (5)

Detroit, Michigan, 48201, United States

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Nevada Cancer Institute Dept. of Nevada Cancer (3)

Las Vegas, Nevada, 89135, 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, 75038, United States

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Seattle Cancer Care Alliance Dept. of SCCA

Seattle, Washington, 98105, United States

Location

Novartis Investigative Site

Brussels, 1070, Belgium

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Novartis Investigative Site

Brussels, 1200, Belgium

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Novartis Investigative Site

Charleroi, 6000, Belgium

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Novartis Investigative Site

Kortrijk, 8500, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Liège, 4000, Belgium

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Novartis Investigative Site

Rio de Janeiro, Rio de Janeiro, 20230-130, Brazil

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90560-030, Brazil

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Novartis Investigative Site

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

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Novartis Investigative Site

Ribeirão Preto, São Paulo, 14015-130, Brazil

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Novartis Investigative Site

Santo André, São Paulo, 09060-650, Brazil

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Novartis Investigative Site

São Paulo, São Paulo, 01246-000, Brazil

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Novartis Investigative Site

Olomouc, 775 20, Czechia

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Novartis Investigative Site

Prague, 140 00, Czechia

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Novartis Investigative Site

Cairo, Egypt, Egypt

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Novartis Investigative Site

Cairo, Egypt

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Novartis Investigative Site

Strasbourg, Cedex, 67091, France

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Novartis Investigative Site

Suresnes, France, 92150, France

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Avignon, 84000, France

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Bordeaux, 33075, France

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Caen, 14021, France

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La Roche-sur-Yon, 85925, France

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Montellier Cedex 5, 34298, France

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Nantes, 44202, France

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Reims, 51100, France

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Rouen, 76031, France

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Strasbourg, 67010, France

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Toulouse, 31059, France

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Berlin, 10117, Germany

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Berlin, 13055, Germany

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Dessau, 06846, Germany

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Essen, 45122, Germany

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Frankfurt, 60488, Germany

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Frankfurt, 60590, Germany

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Göttingen, 37075, Germany

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Hamburg, 20246, Germany

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Hanover, 30625, Germany

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Heidelberg, 69115, Germany

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Leipzig, 04109, Germany

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Mainz, 55131, Germany

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Tübingen, 72076, 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, 1086, Hungary

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Novartis Investigative Site

Budapest, 1122, Hungary

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Brescia, BS, 25123, Italy

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Cremona, CR, 26100, Italy

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Catanzaro, CZ, 88100, Italy

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Florence, FI, 50134, Italy

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Milan, MI, 20133, Italy

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Modena, MO, 41100, Italy

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Perugia, PG, 06129, Italy

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Aviano, PN, 33081, Italy

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Pavia, PV, 27100, Italy

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Roma, RM, 00128, Italy

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Roma, RM, 00152, Italy

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Trento, TN, 38100, Italy

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Negrar, VR, 37024, Italy

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Napoli, 80131, Italy

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Leiden, Netherlands, 2333 ZA, Netherlands

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Novartis Investigative Site

Moscow, Moscow, 115478, Russia

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Novartis Investigative Site

Obninsk, Russia, 249036, Russia

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Novartis Investigative Site

Moscow, 125284, Russia

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Novartis Investigative Site

Saint Petersburg, 191104, Russia

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Novartis Investigative Site

Saint Petersburg, 197758, Russia

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Novartis Investigative Site

Singapore, Singapore, 258500, Singapore

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Novartis Investigative Site

Johannesburg, 2196, South Africa

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Pretoria, 0001, South Africa

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Novartis Investigative Site

Pretoria, 0044, South Africa

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Novartis Investigative Site

Goyang-si, Gyeonggi-do, 03722, South Korea

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Novartis Investigative Site

Seoul, Korea, 06351, South Korea

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Novartis Investigative Site

Daegu, 705-703, South Korea

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Novartis Investigative Site

Seoul, 136-705, South Korea

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Novartis Investigative Site

Taegu, 700 -721, South Korea

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Novartis Investigative Site

Jaén, Andalusia, 23007, Spain

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Novartis Investigative Site

Barcelona, Barcelona, 08041, Spain

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Novartis Investigative Site

Santander, Cantabria, 39008, Spain

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Novartis Investigative Site

Madrid, Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, Madrid, 28041, Spain

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Zaragoza, Zaragoza, 50009, Spain

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Santander, 39008, Spain

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Bern, Switzerland, 3010, Switzerland

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Chur, 7000, Switzerland

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Taichung, Taiwan, 40705, Taiwan

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Novartis Investigative Site

Taipei, Taiwan, 10002, Taiwan

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Novartis Investigative Site

Taipei, Taiwan, 114, Taiwan

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Novartis Investigative Site

Taipei, Taiwan, ROC, 112, Taiwan

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Novartis Investigative Site

Linkou District, 33305, Taiwan

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Novartis Investigative Site

Bangkok, 10330, Thailand

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Songkhla, 90110, Thailand

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Adana, Turkey, 01330, Turkey (Türkiye)

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Novartis Investigative Site

Ankara, Turkey, 06100, Turkey (Türkiye)

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Novartis Investigative Site

Bursa, Turkey, 16059, Turkey (Türkiye)

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Altunizade, 34662, Turkey (Türkiye)

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Antalya, 07070, Turkey (Türkiye)

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Novartis Investigative Site

Balcova / Izmir, 35340, Turkey (Türkiye)

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Novartis Investigative Site

Mecidiyekoy/Istanbul, 34394, Turkey (Türkiye)

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Novartis Investigative Site

Northwood, Middlesex, HA6 2RN, United Kingdom

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Novartis Investigative Site

Glasgow, G12 0YN, United Kingdom

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Novartis Investigative Site

Southampton, SO16 6YD, United Kingdom

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Related Publications (2)

• 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.

  PMID: 37146227 DERIVED

• 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.

  PMID: 25851632 DERIVED

Related Links

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

MeSH Terms

Conditions

Carcinoma; Adenocarcinoma; Carcinoma, Renal Cell; Margins of Excision

Interventions

Everolimus; Interferon alpha-2; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2008
• First Posted: July 21, 2008
• Study Start: November 12, 2008
• Primary Completion: December 31, 2011
• Study Completion: April 15, 2013
• Last Updated: March 20, 2017
• Results First Posted: May 7, 2014

Record last verified: 2017-02

Locations

BE (6); EG (2); HU (2); CH (2); TW (5); TH (2); IT (14); BR (6); RU (5); KR (5); NL (1); CZ (2); SG (1); DE (13); ZA (3); HK (2); US (9); ES (7); TU (7); GB (3); FR (12)