AzTrials
AzTrials

SarcomaPhase 2NCT00643565

A Study of Avastin (Bevacizumab) in Combination With Standard Chemotherapy in Children and Adolescents With Sarcoma.

A Phase 2 study testing Standard chemotherapy and bevacizumab [Avastin] in people with Sarcoma, run by Hoffmann-La Roche at 61 sites in 14 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

This open-label two-arm study will assess the safety and efficacy of a combination of bevacizumab + standard chemotherapy with standard chemotherapy alone as active comparator in childhood and adolescent patients with metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma. Read more about this study

Who is it for?
Ages 6 months to 18 years
Conditions the study is for
Sarcoma
What is being tested?
Standard chemotherapy and bevacizumab [Avastin]
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
154 participants
Where
61 sitesin 14 countries
Study dates
29 Jul 2008to 30 Apr 2019
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 6 months to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • childhood and adolescent patients aged >/=6 months to 18 years of age
  • metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma
  • adequate bone marrow function
  • adequate renal and liver function
  • adequate blood clotting

Who cannot join

  • previous malignant tumors
  • tumor invading major blood vessels
  • prior systemic anti-tumor treatment

Trial locations and contacts

61 sites in 14 countries.

61 sites in 14 countries

United Kingdom11 sites

  • Birmingham Childrens Hospital; Oncology Dept

    Birmingham, B4 6NH

  • Bristol Royal Hospital For Children

    Bristol, BS2 8BJ

  • Royal Hospital for Sick Children

    Edinburgh, EH91LF

  • Royal Hospital For Children

    Glasgow, G51 4TF

  • St. James's University Hospital; Leeds Regional Paediatric Oncology Unit

    Leeds, LS9 7TF

  • Alder Hey Children s Hospital; Department of Pediatrics

    Liverpool, L12 2AP

  • Great Ormond Street Hospital; Dept. Of Pediatric Oncology

    London, WC1N 3JH

  • Royal Manchester Children's Hospital

    Manchester, M27 4HA

  • The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit

    Newcastle upon Tyne, NE1 4LP

  • University Hospital Queens Medical Centre; Department of Paediatric Oncology

    Nottingham, NG7 2UH

  • Royal Marsden Hospital; Pediatric Unit

    Surrey, SM2 5PT

Other trials in United Kingdom

France10 sites

  • CHU Bordeaux; Unite Onco-Hematologie Pediatrique

    Bordeaux, 33076

  • Centre Oscar Lambret; Service de Pediatrie

    Lille, 59020

  • Centre Leon Berard; Pediatrie

    Lyon, 69373

  • Hopital Timone Enfants; Onco Pediatrie

    Marseille, 13385

  • Chr De Nantes; Service D'oncologie Pediatrique

    Nantes, 44093

  • Institut Curie; Oncologie Medicale

    Paris, 75231

  • CHU Hopital Sud; Service d'Hematologie Pediatrique

    Rennes, 35203

  • Hopital Des Enfants; Service d Hemato-Oncologie

    Toulouse, 31059

  • CHU Hopital d Enfants; Centre hospitalier Universitaire Nancy

    Vandœuvre-lès-Nancy, 54511

  • Institut Gustave Roussy; Service Pediatrique

    Villejuif, 94805

Other trials in France

Brazil6 sites

  • Hospital de Cancer de Barretos

    Barretos, São Paulo, 14784-400

  • Clinica de Oncologia de Porto Alegre - CliniOnco

    Porto Alegre, Rio Grande do Sul, 90430-090

  • Instituto Nacional do Cancer - INCA

    Rio de Janeiro, Rio de Janeiro, 20560-120

  • Instituto de Oncologia Pediatrica

    São Paulo, São Paulo, 04023-062

  • ITACI - Instituto de Tratamento do Cancer Infantil

    São Paulo, São Paulo, 05410-030

  • Hospital Santa Marcelina

    São Paulo, São Paulo, 08270-070

Other trials in Brazil

Italy6 sites

  • U.O.A University Onco-Ematologia Pedicatria; Azienda Ospedaliera A.Meyer

    Florence, Tuscany, 50132

  • Istituto Gaslini Ospedale Pediatrico; Dipartimento di Oncoematologia pediatrica

    Genoa, Liguria, 16148

  • Istituto Nazionale Tumori di Milano; S.C. Oncologia Pediatrica

    Milan, Lombardy, 20133

  • Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica

    Padova, Veneto, 35128

  • Ospedale Pediatrico Bambino Gesu

    Rome, Lazio, 00165

  • Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita

    Turin, Piedmont, 10126

Other trials in Italy

Spain6 sites

  • Hospital de Cruces

    Barakaldo, Vizcaya, 48903

  • Hospital Universitari Vall d'Hebron; Servicio de Nefrologia

    Barcelona, 08035

  • Hospital Infantil Universitario Nino Jesus

    Madrid, 28009

  • Hospital Regional Universitario Carlos Haya;Servicio Oncologia Pediatrica

    Málaga, 29011

  • Hospital Universitario Virgen del Rocio; Servicio de Onco-Hematologia Pediatrica

    Seville, 41 41013

  • Hospital Universitario La Fe

    Valencia, 46014

Other trials in Spain

Israel4 sites

  • Soroka Medical Center

    Beersheba, 8410101

  • Rambam Health Care Campus; Pediatric Hematology Oncology Department

    Haifa, 31096

  • Schneider Children's Medical Center

    Petah Tikva, 49100

  • Tel Aviv Sourasky MC, Dana Children's Hospital; Pediatric Hemato-Oncology Clinic

    Tel Aviv, 64239

Other trials in Israel

Belgium3 sites

  • Hôpital Enfants Reine Fabiola

    Brussels, 1020

  • Cliniques Universitaires St-Luc

    Brussels, 1200

  • UZ Gent

    Ghent, 9000

Other trials in Belgium

Germany3 sites

  • University Hospital Essen; Department of Pediatric Oncology

    Essen, 45122

  • Universitaetsklinikum Freiburg - PS; Partnersite - Onkologie

    Freiburg im Breisgau, 79106

  • Universitatsklinikum Munster; Padiatrische Hamatologie und Onkologie

    Münster, 48149

Other trials in Germany

Netherlands3 sites

  • Emma Kinderziekenhuis; Dept of Pediatric Oncology

    Amsterdam, 1105 AZ

  • Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology

    Rotterdam, 3015 GJ

  • Prinses Maxima Centrum

    Utrecht, 3584 CS

Other trials in Netherlands

Canada2 sites

  • Pavillion Chul-Chuq

    Sainte-Foy, Quebec, G1V 4G2

  • Hospital For Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

Czechia2 sites

  • Fakultni nemocnice Brno

    Brno, 613 00

  • Fakultni nemocnice v Motole

    Prague, 150 06

Other trials in Czechia

Poland2 sites

  • Uniwersytet Medyczny W Lublinie; Klinika Hematologii i Onkologii Dzieciecej

    Lublin, 20-093

  • Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii

    Warsaw, 04-746

Other trials in Poland

Russia2 sites

  • Center for Children's Hematology, Oncology and Immunology

    Moscow, 117198

  • Saint-Petersburg SHI City Clinical Hospital #31

    Saint Petersburg, 197110

Other trials in Russia

Chile1 site

  • Hospital Luis Calvo Mackenna; Oncologia

    Santiago, 7500539

Other trials in Chile

About this study

Official title: An Open-label, Multi-center, Randomized Study of the Safety and Effect on Event-free Survival of Bevacizumab in Combination With Standard Chemotherapy in Childhood and Adolescent Patients With Metastatic Rhabdomyosarcoma and Non-rhabdomyosarcoma Soft Tissue Sarcoma

This open-label two-arm study will assess the safety and efficacy of a combination of bevacizumab + standard chemotherapy with standard chemotherapy alone as active comparator in childhood and adolescent patients with metastatic rhabdomyosarcoma or non-rhabdomyosarcoma soft tissue sarcoma. Patients will be randomized to receive bevacizumab + standard chemotherapy or standard chemotherapy alone. Treatment will consist of 9 x 3-week cycles of induction treatment (standard chemotherapy with or without bevacizumab 7.5 mg/kg iv on day 1 of each cycle) followed by 12 x 4-week cycles of maintenance treatment (standard chemotherapy with or without bevacizumab 5 mg/kg iv on days 1 and 15 of each cycle). The anticipated time on study treatment is 1-2 years.

Conditions
Sarcoma
Being tested
Standard chemotherapy, bevacizumab [Avastin]
Medical subject headings
Sarcoma

What participants receive

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

  • Standard chemotherapyDrug

    As prescribed

  • bevacizumab [Avastin]Drug

    7.5 mg/kg iv on day 1 of 9 x 3-week cycles, followed by 5 mg/kg iv on days 1 and 15 of each 4-week cycle

Study groups in NCT00643565
Study groupRoleWhat they receive
Bevacizumab + ChemotherapyExperimentalParticipants received continuous IV infusion of bevacizumab (7.5 mg/kg every 3 weeks) on Day 1 of 3-week cycles followed by induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy) as per institutional practice for a total of 9 cycles during induction treatment phase. As per the investigator decision, local therapy (radiotherapy and /or surgery) was expected to start after 4 weeks of the last bevacizumab administration in the induction phase and resumed to bevacizumab in the maintenance phase at least 4 weeks after the last dose of local therapy. During maintenance treatment phase, participants received IV infusion of bevacizumab (5 mg/kg every 2 weeks) followed by vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Days 1 and 15 of 4-week cycles for a total of 12 cycles.
Receives: Drug: Standard chemotherapy; Drug: bevacizumab [Avastin]
ChemotherapyActive comparatorParticipants received 9 cycles of induction chemotherapy (4 cycles of IVADo-containing chemotherapy followed by 5 cycles of IVA-containing chemotherapy administered every 3 weeks as per institutional practice. As per the investigator evaluation, participants had option to undergo local therapy (radiotherapy and /or surgery) during last 3 cycles of IVA (i.e. from Cycle 6 to Cycle 9). During maintenance treatment phase, participants received vinorelbine- and cyclophosphamide-containing chemotherapy (as per institutional practice) on Day 1 and 15 of 4-week cycles for a total of 12 cycles.
Receives: Drug: Standard chemotherapy

What is being measured

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

  1. Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment

    EFS events included tumor progression (IRC assessed), no evidence of response after 3 cycles of induction (derived from IRC assessment), second primary cancer, or death due to any cause. Data for participants who had not experienced an event by the time of clinical cut-off were censored at the date of the last disease assessment prior to the clinical cut-off date. Data for participants who did not have any post-baseline disease assessments were censored at the time of randomization. Tumor progression was defined using Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) as at least a 20% increase in the disease measurement, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions, or evidence of clinical progression and unequivocal progression of existing non-target lesions.

    Measured: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)

  2. EFS Duration as Per IRC Assessment

    EFS was defined as the time between randomization and occurrence of EFS event. EFS events are described in Outcome Measure 1. Median EFS was estimated using Kaplan-Meier estimates and 95% confidence intervals (CI) for median was computed using the method of Brookmeyer and Crowley.

    Measured: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)

Secondary outcomes (9)

  1. Percentage of Participants With Objective Response Prior to First Local Therapy Assessed by RECIST v1.0 Criteria

    Objective response prior to first local therapy (surgery and/or radiotherapy) was defined as complete response (CR) or partial response (PR) determined on two consecutive occasions >/=4 weeks apart. Tumor response was assessed as per IRC using RECIST v1.0. CR was defined as disappearance of all target and non-target lesions. If immunocytology was available, no disease was to be detected by that methodology. PR was defined as at least a 30% decrease in the disease measurement, taking as reference the disease measurement done to confirm measurable disease at study entry.

    Measured: Screening up to approximately 6.75 years

  2. Percentage of Participants Who Experienced EFS Events Among Participants Who Had Objective Response

    EFS events was described in Outcome Measure 1 and Outcome Measure 3.

    Measured: Screening up to approximately 6.75 years

  3. Duration of Response

    Duration of Response was defined as time between first objective response and the occurrence of an EFS event (described in Outcome Measure 1). Objective response was defined in Outcome Measure 3. Median duration of response was estimated using Kaplan-Meier estimates and 95% CI for median was computed using the method of Brookmeyer and Crowley.

    Measured: Screening up to approximately 6.75 years

  4. Percentage of Participants Who Died

    Measured: Screening up to approximately 10.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years.

  5. Overall Survival Duration

    Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Median overall survival was estimated using Kaplan-Meier estimates and 95% CI for median was computed using the method of Brookmeyer and Crowley.

    Measured: Screening up to approximately 10.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)

  6. Area Under the Curve at Steady State (AUCss) of Bevacizumab

    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. AUCss is expressed in milligrams times days per milliliter (mg*day/mL).

    Measured: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase

  7. Volume of Distribution of Bevacizumab

    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

    Measured: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks)

  8. Half-Life of Bevacizumab

    Half-life is the time measured for the plasma concentration to decrease by one half.

    Measured: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks)

  9. Clearance of Bevacizumab

    CL is a quantitative measure of the rate at which a drug substance is removed from the body. CL is expressed in milliliters per day (mL/day).

    Measured: Pre- and within 3 hours post-dose on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycle 2-4 of induction phase (1 cycle = 3 weeks)

Timeline

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

  1. First posted26 Mar 2008 (estimated)
  2. Study start29 Jul 2008
  3. Primary completion31 May 2015
  4. Study completion30 Apr 2019

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
154 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00643565
Sponsor's protocol ID
BO20924
Other IDs
2007-005017-19
Status last verified
Oct 2019
First submitted
20 Mar 2008
Last updated
22 Oct 2019

Publications

  • Schoot RA, Chisholm JC, Casanova M, Minard-Colin V, Geoerger B, Cameron AL, Coppadoro B, Zanetti I, Orbach D, Kelsey A, Rogers T, Guizani C, Elze M, Ben-Arush M, McHugh K, van Rijn RR, Ferman S, Gallego S, Ferrari A, Jenney M, Bisogno G, Merks JHM. Metastatic Rhabdomyosarcoma: Results of the European Paediatric Soft Tissue Sarcoma Study Group MTS 2008 Study and Pooled Analysis With the Concurrent BERNIE Study. J Clin Oncol. 2022 Nov 10;40(32):3730-3740. doi: 10.1200/JCO.21.02981. Epub 2022 Jun 16.

    PubMed 35709412

  • Ferrari A, Merks JHM, Chisholm JC, Orbach D, Brennan B, Gallego S, van Noesel MM, McHugh K, van Rijn RR, Gaze MN, Martelli H, Bergeron C, Corradini N, Minard-Colin V, Bisogno G, Geoerger B, Caron HN, De Salvo GL, Casanova M. Outcomes of metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated within the BERNIE study: a randomised, phase II study evaluating the addition of bevacizumab to chemotherapy. Eur J Cancer. 2020 May;130:72-80. doi: 10.1016/j.ejca.2020.01.029. Epub 2020 Mar 13.

    PubMed 32179448

  • Chisholm JC, Merks JHM, Casanova M, Bisogno G, Orbach D, Gentet JC, Thomassin-Defachelles AS, Chastagner P, Lowis S, Ronghe M, McHugh K, van Rijn RR, Hilton M, Bachir J, Furst-Recktenwald S, Geoerger B, Oberlin O; European paediatric Soft tissue sarcoma Study Group (EpSSG) and the European Innovative Therapies for Children with Cancer (ITCC) Consortium. Open-label, multicentre, randomised, phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study). Eur J Cancer. 2017 Sep;83:177-184. doi: 10.1016/j.ejca.2017.06.015. Epub 2017 Aug 23.

    PubMed 28738258

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard chemotherapy and bevacizumab [Avastin] in people with Sarcoma, run by Hoffmann-La Roche at 61 sites in 14 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 5 inclusion and 3 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 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in United Kingdom, France, Brazil, Italy, Spain and 9 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 12 Feb 2016). 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?

Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment (time frame: Screening up to approximately 6.75 years (assessed at screening, Cycles 4, 7 of induction phase, Cycles 1, 4, 7, 10 of maintenance, then every 3 months for 1.5 years and thereafter every 6 months for 2.5 years)). The study lists 2 primary outcomes in all. 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 NCT00643565, which also lists 3 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 22 Oct 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in