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

NCT00643565 | Completed Phase 2 Results

• 2 other identifiers: BO209242007-005017-19
• Study Type: interventional
• Target: 154
• Locations: 14 countries
• Sites: 61

Brief 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. 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

Outcome Measures

Primary Outcomes (2)

• 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.

  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)

• 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.

  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)

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

  Screening up to approximately 6.75 years

• Percentage of Participants Who Experienced EFS Events Among Participants Who Had Objective Response

  Screening up to approximately 6.75 years

• Duration of Response

  Screening up to approximately 6.75 years

• Percentage of Participants Who Died

  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.

• Overall Survival Duration

  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)

Study Arms (2)

Bevacizumab + Chemotherapy

EXPERIMENTAL

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.

Drug: Standard chemotherapy; Drug: bevacizumab [Avastin]

Chemotherapy

ACTIVE COMPARATOR

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.

Drug: Standard chemotherapy

Interventions

Standard chemotherapy DRUG

As prescribed

Bevacizumab + Chemotherapy; Chemotherapy

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

Bevacizumab + Chemotherapy

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (61)

Hôpital Enfants Reine Fabiola

Brussels, 1020, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Instituto Nacional do Cancer - INCA

Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

Location

Clinica de Oncologia de Porto Alegre - CliniOnco

Porto Alegre, Rio Grande do Sul, 90430-090, Brazil

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Instituto de Oncologia Pediatrica

São Paulo, São Paulo, 04023-062, Brazil

Location

ITACI - Instituto de Tratamento do Cancer Infantil

São Paulo, São Paulo, 05410-030, Brazil

Location

Hospital Santa Marcelina

São Paulo, São Paulo, 08270-070, Brazil

Location

Hospital For Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Pavillion Chul-Chuq

Sainte-Foy, Quebec, G1V 4G2, Canada

Location

Hospital Luis Calvo Mackenna; Oncologia

Santiago, 7500539, Chile

Location

Fakultni nemocnice Brno

Brno, 613 00, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

CHU Bordeaux; Unite Onco-Hematologie Pediatrique

Bordeaux, 33076, France

Location

Centre Oscar Lambret; Service de Pediatrie

Lille, 59020, France

Location

Centre Leon Berard; Pediatrie

Lyon, 69373, France

Location

Hopital Timone Enfants; Onco Pediatrie

Marseille, 13385, France

Location

Chr De Nantes; Service D'oncologie Pediatrique

Nantes, 44093, France

Location

Institut Curie; Oncologie Medicale

Paris, 75231, France

Location

CHU Hopital Sud; Service d'Hematologie Pediatrique

Rennes, 35203, France

Location

Hopital Des Enfants; Service d Hemato-Oncologie

Toulouse, 31059, France

Location

CHU Hopital d Enfants; Centre hospitalier Universitaire Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy; Service Pediatrique

Villejuif, 94805, France

Location

University Hospital Essen; Department of Pediatric Oncology

Essen, 45122, Germany

Location

Universitaetsklinikum Freiburg - PS; Partnersite - Onkologie

Freiburg im Breisgau, 79106, Germany

Location

Universitatsklinikum Munster; Padiatrische Hamatologie und Onkologie

Münster, 48149, Germany

Location

Soroka Medical Center

Beersheba, 8410101, Israel

Location

Rambam Health Care Campus; Pediatric Hematology Oncology Department

Haifa, 31096, Israel

Location

Schneider Children's Medical Center

Petah Tikva, 49100, Israel

Location

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

Tel Aviv, 64239, Israel

Location

Ospedale Pediatrico Bambino Gesu

Rome, Lazio, 00165, Italy

Location

Istituto Gaslini Ospedale Pediatrico; Dipartimento di Oncoematologia pediatrica

Genoa, Liguria, 16148, Italy

Location

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

Milan, Lombardy, 20133, Italy

Location

Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita

Turin, Piedmont, 10126, Italy

Location

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

Florence, Tuscany, 50132, Italy

Location

Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica

Padua, Veneto, 35128, Italy

Location

Emma Kinderziekenhuis; Dept of Pediatric Oncology

Amsterdam, 1105 AZ, Netherlands

Location

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

Rotterdam, 3015 GJ, Netherlands

Location

Prinses Maxima Centrum

Utrecht, 3584 CS, Netherlands

Location

Uniwersytet Medyczny W Lublinie; Klinika Hematologii i Onkologii Dzieciecej

Lublin, 20-093, Poland

Location

Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii

Warsaw, 04-746, Poland

Location

Center for Children's Hematology, Oncology and Immunology

Moscow, 117198, Russia

Location

Saint-Petersburg SHI City Clinical Hospital #31

Saint Petersburg, 197110, Russia

Location

Hospital de Cruces

Barakaldo, Vizcaya, 48903, Spain

Location

Hospital Universitari Vall d'Hebron; Servicio de Nefrologia

Barcelona, 08035, Spain

Location

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

Location

Hospital Regional Universitario Carlos Haya;Servicio Oncologia Pediatrica

Málaga, 29011, Spain

Location

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

Seville, 41 41013, Spain

Location

Hospital Universitario La Fe

Valencia, 46014, Spain

Location

Birmingham Childrens Hospital; Oncology Dept

Birmingham, B4 6NH, United Kingdom

Location

Bristol Royal Hospital For Children

Bristol, BS2 8BJ, United Kingdom

Location

Royal Hospital for Sick Children

Edinburgh, EH91LF, United Kingdom

Location

Royal Hospital For Children

Glasgow, G51 4TF, United Kingdom

Location

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

Leeds, LS9 7TF, United Kingdom

Location

Alder Hey Children s Hospital; Department of Pediatrics

Liverpool, L12 2AP, United Kingdom

Location

Great Ormond Street Hospital; Dept. Of Pediatric Oncology

London, WC1N 3JH, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, M27 4HA, United Kingdom

Location

The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

University Hospital Queens Medical Centre; Department of Paediatric Oncology

Nottingham, NG7 2UH, United Kingdom

Location

Royal Marsden Hospital; Pediatric Unit

Surrey, SM2 5PT, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 35709412 DERIVED

• 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.

  PMID: 32179448 DERIVED

• 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.

  PMID: 28738258 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  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: March 20, 2008
• First Posted: March 26, 2008
• Study Start: July 29, 2008
• Primary Completion: May 31, 2015
• Study Completion: April 30, 2019
• Last Updated: October 22, 2019
• Results First Posted: February 12, 2016

Record last verified: 2019-10

Locations

GB (11); RU (2); FR (10); BE (3); CL (1); DE (3); CA (2); IL (4); NL (3); BR (6); PL (2); CZ (2); IT (6); ES (6)