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

NCT ID: NCT00643565

Last Updated: 2019-10-22

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

154 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-07-29

Study Completion Date

2019-04-30

Brief Summary

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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.

Detailed Description

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Conditions

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Sarcoma

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 + Chemotherapy

Participants 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.

Group Type EXPERIMENTAL

Standard chemotherapy

Intervention Type DRUG

As prescribed

bevacizumab [Avastin]

Intervention Type 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

Chemotherapy

Participants 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.

Group Type ACTIVE_COMPARATOR

Standard chemotherapy

Intervention Type DRUG

As prescribed

Interventions

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Standard chemotherapy

As prescribed

Intervention Type DRUG

bevacizumab [Avastin]

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* previous malignant tumors
* tumor invading major blood vessels
* prior systemic anti-tumor treatment
Minimum Eligible Age

6 Months

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Hôpital Enfants Reine Fabiola

Brussels, , Belgium

Site Status

Cliniques Universitaires St-Luc

Brussels, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

Instituto Nacional do Cancer - INCA

Rio de Janeiro, Rio de Janeiro, Brazil

Site Status

Clinica de Oncologia de Porto Alegre - CliniOnco

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital de Cancer de Barretos

Barretos, São Paulo, Brazil

Site Status

Instituto de Oncologia Pediatrica

São Paulo, São Paulo, Brazil

Site Status

ITACI - Instituto de Tratamento do Cancer Infantil

São Paulo, São Paulo, Brazil

Site Status

Hospital Santa Marcelina

São Paulo, São Paulo, Brazil

Site Status

Hospital For Sick Children

Toronto, Ontario, Canada

Site Status

Pavillion Chul-Chuq

Sainte-Foy, Quebec, Canada

Site Status

Hospital Luis Calvo Mackenna; Oncologia

Santiago, , Chile

Site Status

Fakultni nemocnice Brno

Brno, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

CHU Bordeaux; Unite Onco-Hematologie Pediatrique

Bordeaux, , France

Site Status

Centre Oscar Lambret; Service de Pediatrie

Lille, , France

Site Status

Centre Leon Berard; Pediatrie

Lyon, , France

Site Status

Hopital Timone Enfants; Onco Pediatrie

Marseille, , France

Site Status

Chr De Nantes; Service D'oncologie Pediatrique

Nantes, , France

Site Status

Institut Curie; Oncologie Medicale

Paris, , France

Site Status

CHU Hopital Sud; Service d'Hematologie Pediatrique

Rennes, , France

Site Status

Hopital Des Enfants; Service d Hemato-Oncologie

Toulouse, , France

Site Status

CHU Hopital d Enfants; Centre hospitalier Universitaire Nancy

Vandœuvre-lès-Nancy, , France

Site Status

Institut Gustave Roussy; Service Pediatrique

Villejuif, , France

Site Status

University Hospital Essen; Department of Pediatric Oncology

Essen, , Germany

Site Status

Universitaetsklinikum Freiburg - PS; Partnersite - Onkologie

Freiburg im Breisgau, , Germany

Site Status

Universitatsklinikum Munster; Padiatrische Hamatologie und Onkologie

Münster, , Germany

Site Status

Soroka Medical Center

Beersheba, , Israel

Site Status

Rambam Health Care Campus; Pediatric Hematology Oncology Department

Haifa, , Israel

Site Status

Schneider Children's Medical Center

Petah Tikva, , Israel

Site Status

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

Tel Aviv, , Israel

Site Status

Ospedale Pediatrico Bambino Gesu

Rome, Lazio, Italy

Site Status

Istituto Gaslini Ospedale Pediatrico; Dipartimento di Oncoematologia pediatrica

Genoa, Liguria, Italy

Site Status

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

Milan, Lombardy, Italy

Site Status

Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita

Turin, Piedmont, Italy

Site Status

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

Florence, Tuscany, Italy

Site Status

Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica

Padua, Veneto, Italy

Site Status

Emma Kinderziekenhuis; Dept of Pediatric Oncology

Amsterdam, , Netherlands

Site Status

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

Rotterdam, , Netherlands

Site Status

Prinses Maxima Centrum

Utrecht, , Netherlands

Site Status

Uniwersytet Medyczny W Lublinie; Klinika Hematologii i Onkologii Dzieciecej

Lublin, , Poland

Site Status

Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii

Warsaw, , Poland

Site Status

Center for Children's Hematology, Oncology and Immunology

Moscow, , Russia

Site Status

Saint-Petersburg SHI City Clinical Hospital #31

Saint Petersburg, , Russia

Site Status

Hospital de Cruces

Barakaldo, Vizcaya, Spain

Site Status

Hospital Universitari Vall d'Hebron; Servicio de Nefrologia

Barcelona, , Spain

Site Status

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Site Status

Hospital Regional Universitario Carlos Haya;Servicio Oncologia Pediatrica

Málaga, , Spain

Site Status

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

Seville, , Spain

Site Status

Hospital Universitario La Fe

Valencia, , Spain

Site Status

Birmingham Childrens Hospital; Oncology Dept

Birmingham, , United Kingdom

Site Status

Bristol Royal Hospital For Children

Bristol, , United Kingdom

Site Status

Royal Hospital for Sick Children

Edinburgh, , United Kingdom

Site Status

Royal Hospital For Children

Glasgow, , United Kingdom

Site Status

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

Leeds, , United Kingdom

Site Status

Alder Hey Children s Hospital; Department of Pediatrics

Liverpool, , United Kingdom

Site Status

Great Ormond Street Hospital; Dept. Of Pediatric Oncology

London, , United Kingdom

Site Status

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit

Newcastle upon Tyne, , United Kingdom

Site Status

University Hospital Queens Medical Centre; Department of Paediatric Oncology

Nottingham, , United Kingdom

Site Status

Royal Marsden Hospital; Pediatric Unit

Surrey, , United Kingdom

Site Status

Countries

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Belgium Brazil Canada Chile Czechia France Germany Israel Italy Netherlands Poland Russia Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 35709412 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32179448 (View on PubMed)

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.

Reference Type DERIVED
PMID: 28738258 (View on PubMed)

Other Identifiers

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2007-005017-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BO20924

Identifier Type: -

Identifier Source: org_study_id

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