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

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00643565
• Other study ID #: BO20924
• Secondary ID: 2007-005017-19
• Status: Completed
• Phase: Phase 2
• Start date: July 29, 2008
• Est. completion date: April 30, 2019

Study information

• Verified date: October 2019
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: April 30, 2019
• Est. primary completion date: May 31, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma

Intervention

Drug:
• Standard chemotherapy
As prescribed
• 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

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	Hôpital Enfants Reine Fabiola	Bruxelles
Belgium	UZ Gent	Gent
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Clinica de Oncologia de Porto Alegre - CliniOnco	Porto Alegre	RS
Brazil	Instituto Nacional do Cancer - INCA	Rio de Janeiro	RJ
Brazil	Hospital Santa Marcelina	Sao Paulo	SP
Brazil	Instituto de Oncologia Pediatrica	Sao Paulo	SP
Brazil	ITACI - Instituto de Tratamento do Cancer Infantil	Sao Paulo	SP
Canada	Pavillion Chul-Chuq	Sainte-foy	Quebec
Canada	Hospital For Sick Children	Toronto	Ontario
Chile	Hospital Luis Calvo Mackenna; Oncologia	Santiago
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice v Motole	Praha 5
France	CHU Bordeaux; Unite Onco-Hematologie Pediatrique	Bordeaux
France	Centre Oscar Lambret; Service de Pediatrie	Lille
France	Centre Leon Berard; Pediatrie	Lyon
France	Hopital Timone Enfants; Onco Pediatrie	Marseille
France	Chr De Nantes; Service D'oncologie Pediatrique	Nantes
France	Institut Curie; Oncologie Medicale	Paris
France	CHU Hopital Sud; Service d'Hematologie Pediatrique	Rennes
France	Hopital Des Enfants; Service d Hemato-Oncologie	Toulouse
France	CHU Hopital d Enfants; Centre hospitalier Universitaire Nancy	Vandoeuvre Les Nancy
France	Institut Gustave Roussy; Service Pediatrique	Villejuif
Germany	University Hospital Essen; Department of Pediatric Oncology	Essen
Germany	Universitaetsklinikum Freiburg - PS; Partnersite - Onkologie	Freiburg
Germany	Universitatsklinikum Munster; Padiatrische Hamatologie und Onkologie	Münster
Israel	Soroka Medical Center	Beer Sheva
Israel	Rambam Health Care Campus; Pediatric Hematology Oncology Department	Haifa
Israel	Schneider Children's Medical Center	Petach-Tikva
Israel	Tel Aviv Sourasky MC, Dana Children's Hospital; Pediatric Hemato-Oncology Clinic	Tel Aviv
Italy	U.O.A University Onco-Ematologia Pedicatria; Azienda Ospedaliera A.Meyer	Firenze	Toscana
Italy	Istituto Gaslini Ospedale Pediatrico; Dipartimento di Oncoematologia pediatrica	Genova	Liguria
Italy	Istituto Nazionale Tumori di Milano; S.C. Oncologia Pediatrica	Milano	Lombardia
Italy	Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica	Padova	Veneto
Italy	Ospedale Pediatrico Bambino Gesu	Roma	Lazio
Italy	Dipartimento di Scienze Pediatriche Adolescenza; Osp. Infantile Regina Margherita	Torino	Piemonte
Netherlands	Emma Kinderziekenhuis; Dept of Pediatric Oncology	Amsterdam
Netherlands	Erasmus Mc/Sophia's Childrens Hospital; Dept. of Pediatric Oncology	Rotterdam
Netherlands	Prinses Maxima Centrum	Utrecht
Poland	Uniwersytet Medyczny W Lublinie; Klinika Hematologii i Onkologii Dzieciecej	Lublin
Poland	Instytut Pomnik-Centrum Zdrowia Dziecka; Klinika Onkologii	Warsaw
Russian Federation	Center for Children's Hematology, Oncology and Immunology	Moscow
Russian Federation	Saint-Petersburg SHI City Clinical Hospital #31	St. Petersburg
Spain	Hospital de Cruces	Barakaldo	Vizcaya
Spain	Hospital Universitari Vall d'Hebron; Servicio de Nefrologia	Barcelona
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital Regional Universitario Carlos Haya;Servicio Oncologia Pediatrica	Malaga
Spain	Hospital Universitario Virgen del Rocio; Servicio de Onco-Hematologia Pediatrica	Sevilla
Spain	Hospital Universitario La Fe	Valencia
United Kingdom	Birmingham Childrens Hospital; Oncology Dept	Birmingham
United Kingdom	Bristol Royal Hospital For Children	Bristol
United Kingdom	Royal Hospital for Sick Children	Edinburgh
United Kingdom	Royal Hospital For Children	Glasgow
United Kingdom	St. James's University Hospital; Leeds Regional Paediatric Oncology Unit	Leeds
United Kingdom	Alder Hey Children s Hospital; Department of Pediatrics	Liverpool
United Kingdom	Great Ormond Street Hospital; Dept. Of Pediatric Oncology	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit	Newcastle Upon Tyne
United Kingdom	University Hospital Queens Medical Centre; Department of Paediatric Oncology	Nottingham
United Kingdom	Royal Marsden Hospital; Pediatric Unit	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Belgium,  Brazil,  Canada,  Chile,  Czechia,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Russian Federation,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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.	Screening up to approximately 6.75 years
Secondary	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.	Screening up to approximately 6.75 years
Secondary	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.	Screening up to approximately 6.75 years
Secondary	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.
Secondary	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.	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)
Secondary	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).	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
Secondary	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.	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)
Secondary	Half-Life of Bevacizumab	Half-life is the time measured for the plasma concentration to decrease by one half.	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)
Secondary	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).	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)