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AzTrials

CarcinomaPhase 2NCT00719264

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

A Phase 2 study testing RAD001(everolimus), interferon alfa-2a and bevacizumab in people with Carcinoma and Adenocarcinoma, run by Novartis Pharmaceuticals at 109 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Adenocarcinoma, Renal Cell
What is being tested?
RAD001(everolimus), interferon alfa-2a and bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
365 participants
Where
109 sitesin 21 countries
Study dates
12 Nov 2008to 15 Apr 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • Adequate liver function
  • Adequate renal function
  • Adequate coagulation profile

Who cannot join

  • 4 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.
Show all 25Show fewer
  • 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.
  • Patients with a known history of HIV
  • Patients with hypersensitivity to interferon alfa-2a or any component of the product.
  • Patients with an active, bleeding diathesis or coagulopathy or recurrent thromboembolism
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions
  • Left Ventricular Ejection Fraction < lower limit of institutional normal assessed by ECHO or MUGA
  • Patients who have a history of another primary malignancy ≤ 3 years
  • Female patients who are pregnant or breast feeding
  • Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
  • Patients unwilling to or unable to comply with the protocol
  • Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

109 sites in 21 countries.

109 sites in 21 countries

Italy14 sites

  • Novartis Investigative Site

    Aviano, PN, 33081

  • Novartis Investigative Site

    Brescia, BS, 25123

  • Novartis Investigative Site

    Catanzaro, CZ, 88100

  • Novartis Investigative Site

    Cremona, CR, 26100

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Milan, MI, 20133

  • Novartis Investigative Site

    Modena, MO, 41100

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Negrar, VR, 37024

  • Novartis Investigative Site

    Pavia, PV, 27100

  • Novartis Investigative Site

    Perugia, PG, 06129

  • Novartis Investigative Site

    Roma, RM, 00128

  • Novartis Investigative Site

    Roma, RM, 00152

  • Novartis Investigative Site

    Trento, TN, 38100

Other trials in Italy

Germany13 sites

  • Novartis Investigative Site

    Berlin, 10117

  • Novartis Investigative Site

    Berlin, 13055

  • Novartis Investigative Site

    Dessau, 06846

  • Novartis Investigative Site

    Essen, 45122

  • Novartis Investigative Site

    Frankfurt, 60488

  • Novartis Investigative Site

    Frankfurt, 60590

  • Novartis Investigative Site

    Göttingen, 37075

  • Novartis Investigative Site

    Hamburg, 20246

  • Novartis Investigative Site

    Hanover, 30625

  • Novartis Investigative Site

    Heidelberg, 69115

  • Novartis Investigative Site

    Leipzig, 04109

  • Novartis Investigative Site

    Mainz, 55131

  • Novartis Investigative Site

    Tübingen, 72076

Other trials in Germany

France12 sites

  • Novartis Investigative Site

    Avignon, 84000

  • Novartis Investigative Site

    Bordeaux, 33075

  • Novartis Investigative Site

    Caen, 14021

  • Novartis Investigative Site

    La Roche-sur-Yon, 85925

  • Novartis Investigative Site

    Montellier Cedex 5, 34298

  • Novartis Investigative Site

    Nantes, 44202

  • Novartis Investigative Site

    Reims, 51100

  • Novartis Investigative Site

    Rouen, 76031

  • Novartis Investigative Site

    Strasbourg, Cedex, 67091

  • Novartis Investigative Site

    Strasbourg, 67010

  • Novartis Investigative Site

    Suresnes, France, 92150

  • Novartis Investigative Site

    Toulouse, 31059

Other trials in France

United States9 sites

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

    Bethlehem, Pennsylvania

  • Karmanos Cancer Institute Dept.of KarmanosCancerInst (5)

    Detroit, Michigan, 48201

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

    Duarte, California, 91010-3000

  • Highlands Oncology Group Dept of Highlands Oncology Grp

    Fayetteville, Arkansas, 72703

  • Las Colinas Hematology Oncology Grapevine

    Irving, Texas, 75038

  • Nevada Cancer Institute Dept. of Nevada Cancer (3)

    Las Vegas, Nevada, 89135

  • USC/Kenneth Norris Comprehensive Cancer Center Regulatory Contact 3

    Los Angeles, California, 90053

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

    Los Angeles, California, 90095

  • Seattle Cancer Care Alliance Dept. of SCCA

    Seattle, Washington, 98105

Other trials in United States

Spain7 sites

  • Novartis Investigative Site

    Barcelona, Barcelona, 08041

  • Novartis Investigative Site

    Jaén, Andalusia, 23007

  • Novartis Investigative Site

    Madrid, Madrid, 28034

  • Novartis Investigative Site

    Madrid, Madrid, 28041

  • Novartis Investigative Site

    Santander, Cantabria, 39008

  • Novartis Investigative Site

    Santander, 39008

  • Novartis Investigative Site

    Zaragoza, Zaragoza, 50009

Other trials in Spain

Turkey (Türkiye)7 sites

  • Novartis Investigative Site

    Adana, Turkey, 01330

  • Novartis Investigative Site

    Altunizade, 34662

  • Novartis Investigative Site

    Ankara, Turkey, 06100

  • Novartis Investigative Site

    Antalya, 07070

  • Novartis Investigative Site

    Balcova / Izmir, 35340

  • Novartis Investigative Site

    Bursa, Turkey, 16059

  • Novartis Investigative Site

    Mecidiyekoy/Istanbul, 34394

Other trials in Turkey (Türkiye)

Belgium6 sites

  • Novartis Investigative Site

    Brussels, 1070

  • Novartis Investigative Site

    Brussels, 1200

  • Novartis Investigative Site

    Charleroi, 6000

  • Novartis Investigative Site

    Kortrijk, 8500

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Liège, 4000

Other trials in Belgium

Brazil6 sites

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90560-030

  • Novartis Investigative Site

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Novartis Investigative Site

    Ribeirão Preto, São Paulo, 14015-130

  • Novartis Investigative Site

    Rio de Janeiro, Rio de Janeiro, 20230-130

  • Novartis Investigative Site

    Santo André, São Paulo, 09060-650

  • Novartis Investigative Site

    São Paulo, São Paulo, 01246-000

Other trials in Brazil

Russia5 sites

  • Novartis Investigative Site

    Moscow, Moscow, 115478

  • Novartis Investigative Site

    Moscow, 125284

  • Novartis Investigative Site

    Obninsk, Russia, 249036

  • Novartis Investigative Site

    Saint Petersburg, 191104

  • Novartis Investigative Site

    Saint Petersburg, 197758

Other trials in Russia

South Korea5 sites

  • Novartis Investigative Site

    Daegu, 705-703

  • Novartis Investigative Site

    Goyang-si, Gyeonggi-do, 03722

  • Novartis Investigative Site

    Seoul, Korea, 06351

  • Novartis Investigative Site

    Seoul, 136-705

  • Novartis Investigative Site

    Taegu, 700 -721

Other trials in South Korea

Taiwan5 sites

  • Novartis Investigative Site

    Linkou District, 33305

  • Novartis Investigative Site

    Taichung, Taiwan, 40705

  • Novartis Investigative Site

    Taipei, Taiwan, 10002

  • Novartis Investigative Site

    Taipei, Taiwan, 114

  • Novartis Investigative Site

    Taipei, Taiwan, ROC, 112

Other trials in Taiwan

South Africa3 sites

  • Novartis Investigative Site

    Johannesburg, 2196

  • Novartis Investigative Site

    Pretoria, 0001

  • Novartis Investigative Site

    Pretoria, 0044

Other trials in South Africa

United Kingdom3 sites

  • Novartis Investigative Site

    Glasgow, G12 0YN

  • Novartis Investigative Site

    Northwood, Middlesex, HA6 2RN

  • Novartis Investigative Site

    Southampton, SO16 6YD

Other trials in United Kingdom

Czechia2 sites

  • Novartis Investigative Site

    Olomouc, 775 20

  • Novartis Investigative Site

    Prague, 140 00

Other trials in Czechia

Egypt2 sites

  • Novartis Investigative Site

    Cairo, Egypt

  • Novartis Investigative Site

    Cairo

Other trials in Egypt

Hong Kong2 sites

  • Novartis Investigative Site

    Shatin, New Territories, Hong Kong

  • Novartis Investigative Site

    Tuenmen, Hong Kong

Other trials in Hong Kong

Hungary2 sites

  • Novartis Investigative Site

    Budapest, 1086

  • Novartis Investigative Site

    Budapest, 1122

Other trials in Hungary

Switzerland2 sites

  • Novartis Investigative Site

    Bern, Switzerland, 3010

  • Novartis Investigative Site

    Chur, 7000

Other trials in Switzerland

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10330

  • Novartis Investigative Site

    Songkhla, 90110

Other trials in Thailand

Netherlands1 site

  • Novartis Investigative Site

    Leiden, Netherlands, 2333 ZA

Other trials in Netherlands

Singapore1 site

  • Novartis Investigative Site

    Singapore, Singapore, 258500

Other trials in Singapore

About this study

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

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.

Being tested
RAD001(everolimus), interferon alfa-2a, bevacizumab
Keywords
Renal cell carcinoma, Adults, Bevacizumab, RAD001, Everolimus, Interferon, Clear, Roferon, Avastin, Nephrectomy, newly diagnosed
Medical subject headings
Carcinoma, Adenocarcinoma, Carcinoma, Renal Cell, Margins of Excision

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RAD001(everolimus)Drug

    Also called Afinitor

    10 mg qd

  • interferon alfa-2aDrug

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

  • bevacizumabDrug

    10 mg/kg every 2 weeks

Study groups in NCT00719264
Study groupRoleWhat they receive
bevacizumab, RAD001 (everolimus)ExperimentalParticipants received oral everolimus 10 mg qd plus intravenous bevacizumab 10mg/kg every 2 weeks
Receives: Drug: RAD001(everolimus); Drug: bevacizumab
bevacizumab, interferon alfa-2a (IFN)Active comparatorParticipants 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
Receives: Drug: interferon alfa-2a; Drug: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

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

    Overall survival (OS) was defined as the time of randomization to the date of death due to any cause.

    Measured: 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)

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

    Overall response is defined as the number of participants having achieved confirmed Complete Response (CR) + Partial Response (PR). Confirmed CR = at least two determinations of CR at least 4 weeks apart before progression. Confirmed PR = at least two determinations of PR or better at least 4 weeks apart before progression. CR required a disappearance of all target and non-target lesions. PR required at least a 30% decrease in the sum of the longest diameters of all target lesions, taking as a reference the baseline sum of the longest diameters. 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.

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

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

    The duration of response, applied only to participants with best overall response at CR or PR, is defined as the number of days between the date of first documented response (CR or PR) and the date of the event: radiological progression as per central review or death due to underlying cancer, whichever occurs first. If no event, participant is censored at the last adequate assessment.

    Measured: 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.

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

    Participants were monitored for adverse events, serious adverse events and deaths throughout the study. Participants were assessed continuously at each 28-day cycle.

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

  5. 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

    The analysis of this outcome measure was based on the FKSI-DRS scale which is a validated disease-related symptom index containing 9 items that measure symptoms predominantly related to kidney cancer. Each item is scored on a 5-point scale (0 = not at all; 4 = very much). If at least 5 of the 9 questions have been answered, the FKSI-DRS total score is calculated by subtracting nine times the mean of the scores of the answered items from 36. Participants with less than 5 out of the 9 questions answered will have a missing FKSI-DRS total score. The FKSI-DRS total score ranges from 0 (most severe symptoms) to 36 (no symptoms). Definitive deterioration is defined as a decrease by at least 2 units compared to baseline, with no later increase above this threshold observed during the study. A single measure reporting a decrease of at least 2 units was considered definitive only if it is the last one available for the participant.

    Measured: 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

  6. Time to Definitive Deterioration of the Global Health Status and the Physical Functioning (PF) Subscale Scores of the European Organization for the Research and Treatment of Cancer (EORTC)-Core Quality of Life Questionnaire (QLQ-C30) by at Least 10%

    The EORTC QLQ-C30 contains 30 items. These include five functional scales (physical, role, emotional, social and cognitive functioning), three symptom scales (fatigue, pain, nausea, and vomiting), a global health status/QoL scale, and six single items (dyspnea, diarrhea, constipation, anorexia, insomnia and financial impact). The PF subscale consists of 5 questions each scored from 1 (not at all) to 4 (very much). The score for the PF subscale and global health status range from 0 to 100, with a higher score representing a high level of functioning/high quality of life. Definitive deterioration by at least 10% is defined as a decrease in score by at least 10% compared to baseline, with no later increase above this threshold observed during the course of the study. A single measure reporting a decrease of at least 10% is considered definitive only if it is the last one available for the participant.

    Measured: 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 participant randomized until 31Dec2011

  7. Duration of Exposure of RAD001 in Participants Randomized to the Treatment Combination of RAD001 and Bevacizumab

    This outcome measure was assessed continuously.

    Measured: From the date of the first participant treated until the last patient discontinued the study treatment + 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2008 (estimated)
  2. Study start12 Nov 2008
  3. Primary completion31 Dec 2011
  4. Study completion15 Apr 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
365 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00719264
Sponsor's protocol ID
CRAD001L2201
Other IDs
2008-000077-38, 2008
Status last verified
Feb 2017
First submitted
15 Jul 2008
Last updated
20 Mar 2017

Publications

  • 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.

    PubMed 37146227

  • 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.

    PubMed 25851632

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing RAD001(everolimus), interferon alfa-2a and bevacizumab in people with Carcinoma and Adenocarcinoma, run by Novartis Pharmaceuticals at 109 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 109 sites in Italy, Germany, France, United States, Spain and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) of Participants Who Received RAD001 Plus Bevacizumab Versus Participants Who Received IFN Plus Bevacizumab (time frame: 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.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00719264, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Mar 2017.

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