Clinical trial NCT00643565: A Study of Avastin (Bevacizumab) in Combination With Standard Chemotherapy in Children and Adolescents With Sarcoma.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2008-03-26
Enrollment: 154
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Who Experienced Event-Free Survival (EFS) Events as Per Independent Review Committee (IRC) Assessment
timeFrame: 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)
measure: EFS Duration as Per IRC Assessment
timeFrame: 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:
measure: Percentage of Participants With Objective Response Prior to First Local Therapy Assessed by RECIST v1.0 Criteria
timeFrame: Screening up to approximately 6.75 years
measure: Percentage of Participants Who Experienced EFS Events Among Participants Who Had Objective Response
timeFrame: Screening up to approximately 6.75 years
measure: Duration of Response
timeFrame: Screening up to approximately 6.75 years
measure: Percentage of Participants Who Died
timeFrame: 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.
measure: Overall Survival Duration
timeFrame: 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)
measure: Area Under the Curve at Steady State (AUCss) of Bevacizumab
timeFrame: 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
measure: Volume of Distribution of Bevacizumab
timeFrame: 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)
measure: Half-Life of Bevacizumab
timeFrame: 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)
measure: Clearance of Bevacizumab
timeFrame: 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)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Hôpital Enfants Reine Fabiola
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Gent
country: Belgium
facility: UZ Gent
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional do Cancer - INCA
state: RJ
city: Porto Alegre
country: Brazil
facility: Clinica de Oncologia de Porto Alegre - CliniOnco
state: RS
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Oncologia Pediatrica
state: SP
city: Sao Paulo
country: Brazil
facility: ITACI - Instituto de Tratamento do Cancer Infantil
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: SP
city: Toronto
country: Canada
facility: Hospital For Sick Children
state: Ontario
city: Sainte-foy
country: Canada
facility: Pavillion Chul-Chuq
state: Quebec
city: Santiago
country: Chile
facility: Hospital Luis Calvo Mackenna; Oncologia
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Praha 5
country: Czechia
facility: Fakultni nemocnice v Motole
city: Bordeaux
country: France
facility: CHU Bordeaux; Unite Onco-Hematologie Pediatrique
city: Lille
country: France
facility: Centre Oscar Lambret; Service de Pediatrie
city: Lyon
country: France
facility: Centre Leon Berard; Pediatrie
city: Marseille
country: France
facility: Hopital Timone Enfants; Onco Pediatrie
city: Nantes
country: France
facility: Chr De Nantes; Service D'oncologie Pediatrique
city: Paris
country: France
facility: Institut Curie; Oncologie Medicale
city: Rennes
country: France
facility: CHU Hopital Sud; Service d'Hematologie Pediatrique
city: Toulouse
country: France
facility: Hopital Des Enfants; Service d Hemato-Oncologie
city: Vandoeuvre Les Nancy
country: France
facility: CHU Hopital d Enfants; Centre hospitalier Universitaire Nancy
city: Villejuif
country: France
facility: Institut Gustave Roussy; Service Pediatrique
city: Essen
country: Germany
facility: University Hospital Essen; Department of Pediatric Oncology
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg - PS; Partnersite - Onkologie
city: Münster
country: Germany
facility: Universitatsklinikum Munster; Padiatrische Hamatologie und Onkologie
city: Beer Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Rambam Health Care Campus; Pediatric Hematology Oncology Department
city: Petach-Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky MC, Dana Children's Hospital; Pediatric Hemato-Oncology Clinic
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
state: Lazio
city: Genova
country: Italy
facility: Istituto Gaslini Ospedale Pediatrico; Dipartimento di Oncoematologia pediatrica
state: Liguria
city: Milano
country: Italy
facility: Istituto Nazionale Tumori di Milano; S.C. Oncologia Pediatrica
state: Lombardia
city: Torino
country: Italy
facility: Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita
state: Piemonte
city: Firenze
country: Italy
facility: U.O.A University Onco-Ematologia Pedicatria; Azienda Ospedaliera A.Meyer
state: Toscana
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica
state: Veneto
city: Amsterdam
country: Netherlands
facility: Emma Kinderziekenhuis; Dept of Pediatric Oncology
city: Rotterdam
country: Netherlands
facility: Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology
city: Utrecht
country: Netherlands
facility: Prinses Maxima Centrum
city: Lublin
country: Poland
facility: Uniwersytet Medyczny W Lublinie; Klinika Hematologii i Onkologii Dzieciecej
city: Warsaw
country: Poland
facility: Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii
city: Moscow
country: Russian Federation
facility: Center for Children's Hematology, Oncology and Immunology
city: St. Petersburg
country: Russian Federation
facility: Saint-Petersburg SHI City Clinical Hospital #31
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Servicio de Nefrologia
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya;Servicio Oncologia Pediatrica
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio; Servicio de Onco-Hematologia Pediatrica
city: Valencia
country: Spain
facility: Hospital Universitario La Fe
city: Birmingham
country: United Kingdom
facility: Birmingham Childrens Hospital; Oncology Dept
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital For Children
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
city: Glasgow
country: United Kingdom
facility: Royal Hospital For Children
city: Leeds
country: United Kingdom
facility: St. James's University Hospital; Leeds Regional Paediatric Oncology Unit
city: Liverpool
country: United Kingdom
facility: Alder Hey Children s Hospital; Department of Pediatrics
city: London
country: United Kingdom
facility: Great Ormond Street Hospital; Dept. Of Pediatric Oncology
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
city: Nottingham
country: United Kingdom
facility: University Hospital Queens Medical Centre; Department of Paediatric Oncology
city: Surrey
country: United Kingdom
facility: Royal Marsden Hospital; Pediatric Unit
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.