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Effects of Maintenance Cabozantinib+BSC Versus BSC in Children and AYA With Osteosarcoma

Phase 2
Recruiting
Conditions
Osteosarcoma
Osteosarcoma in Children
Osteosarcoma in Adolescents and Young Adults
Interventions
Other: Best Supportive Care (BSC)
Registration Number
NCT06341712
Lead Sponsor
Ipsen
Brief Summary

The participants of this study will be children, adolescents, and young adults with residual osteosarcoma, which cannot be removed completely through surgery.

Participants will have achieved a partial response or stable disease at the end of conventional chemotherapy. Osteosarcoma is cancer of the bone. The cancer cells make immature bone cells, known as osteoid.

Osteosarcoma is very rare, but it is the most common type of bone cancer in children and teens. It is most common in teens and young adults.

In this study, participants will receive either cabozantinib and best supportive care or the best supportive care alone. Best supportive care will be provided at the investigator's discretion and according to institutional guidelines.

It includes antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including radiotherapy), etc. but does not include tumor specific therapy.

Cabozantinib will be taken by mouth (orally), as a tablet, once a day. Cabozantinib will be provided to participants who tolerate it for as long as their disease does not progress. Participants in the study receiving best supportive care alone may switch to treatment with cabozantinib and best supportive care if their disease progresses and if other eligibility criteria are met.

Participants may withdraw consent to participate at any time.

The estimated duration of the study for participants is 24 months, however a participant could remain in the study longer if demonstrating treatment benefit.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
90
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm A: Cabozantinib+ Best supportive care (BSC)Best Supportive Care (BSC)Participants will receive cabozantinib and BSC.
Arm B: Best supportive care (BSC)Best Supportive Care (BSC)Participants will receive BSC alone administered per investigator's discretion and institutional guidelines.
Arm A: Cabozantinib+ Best supportive care (BSC)CabozantinibParticipants will receive cabozantinib and BSC.
Primary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS) assessed by Blinded Independent Radiology Committee (BIRC)From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months).

PFS defined as the time from the date of randomization to the date of first documented disease progression or the date of death due to any cause, whichever occurs first.

Secondary Outcome Measures
NameTimeMethod
Objective response rate (ORR) assessed by BIRCApproximately 34 months after randomization.

ORR defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) determined by BIRC.

Percentage of participants with Treatment Emergent Adverse Event (TEAEs) and Adverse Events of Special Interest (AESIs).From screening to 30 days after last dose.

An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AESIs are AEs that may not be serious but are of special importance to a particular drug or class of drugs.

Disease control rate (DCR) assessed by BIRCApproximately 34 months after randomization.

Defined as the proportion of participants who have achieved CR, PR, or stable disease (SD) determined by BIRC

PFS rate assessed by investigatorAt 4 months and 1 year after randomization.

Defined as the probability that participants have not progressed by investigator assessment and remain alive at 4 months and 1 year.

DCR assessed by investigatorApproximately 34 months after randomization.

Defined as the proportion of participants who have achieved CR, PR, or SD determined by investigator.

Area Under Curve (AUC) at steady state.At Day 1 of week 1 and Day 1 of week 5.
Progression-free survival (PFS) rate assessed by BIRC4 months and 1 year after randomization.

PFS rate at 4 months and 1 year was defined as the probability that participants have not progressed by BIRC assessment and remain alive at 4 months and 1 year.

ORR assessed by investigatorApproximately 34 months after randomization.

Defined as the proportion of participants who have achieved complete response (CR) or partial response (PR) determined by investigator using RECIST version 1.1.

Average concentration (Cavg) at steady stateAt Day 1 of week 1 and Day 1 of week 5.
Change from baseline in European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) (EORTC QLQ-C30) for adult participantsFrom screening to 30 days after last dose.

The EORTC QLQ-C30 was developed by the EORTC Quality of Life Group to assess HRQoL, functioning, and symptoms in cancer clinical trials. It is a 30-item self-administered questionnaire for all cancer types. Final scores range from 0 to 100, with higher scores indicating better health related quality of life. A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

PFS assessed by investigatorFrom randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months).

Defined as the time from the date of randomization to the date of first documented disease progression determined by investigator or the date of death due to any cause, whichever occurs first

Overall survival (OS)From randomization until death or last contact (approximately 34 months).

Defined as the time from date of randomization to the date of death, from any cause

1-year overall survival rateAt 1 year after randomization.

Defined as the probability participants alive at 1 year.

Minimum concentration (Cmin) at steady stateAt Day 1 of week 1 and Day 1 of week 5.
Maximal concentration (Cmax) at steady stateAt Day 1 of week 1 and Day 1 of week 5.
Change from baseline in score for all Paediatric QoL Inventory (PedsQL) Scales including Generic Core Scales and Cancer Modules.From screening to 30 days after last dose.

The PedsQL is a modular instrument designed to measure health-related quality of life in children and adolescent. The PedsQL generic core scales are multidimensional child self-report and parent proxy-report scales developed as the generic core measure to be integrated with the PedsQL. The PedsQL cancer modules was designed to measure paediatric cancer specific HRQoL. Final total scores range from 0 to 100, with higher scores indicating better health related quality of life.

Acceptability and palatability in children and adolescents assessed using a horizontal visual assessment scale.Day of first dose.

Five-point Facial Hedonic Scale (FHS) with a correlated 100-point horizontal Visual Analog Scale (VAS) (FHS/VAS-5) will be used to assess acceptability and palatability in children and adolescents. Final scores range from 0 to 100, with higher scores indicating better palatability and acceptability.

Trial Locations

Locations (74)

Klinikum Dortmund

🇩🇪

Dortmund, Germany

Karolinska University Hospital

🇸🇪

Stockholm, Sweden

AP-HP Hopital Cochin

🇫🇷

Paris, France

CHU de Toulouse - Hôpital des Enfants

🇫🇷

Toulouse, France

Gustave Roussy

🇫🇷

Villejuif, France

Charité - Kinderonkologie

🇩🇪

Berlin, Germany

Institut Curie

🇫🇷

Paris, France

CHU de Poitiers (Poitiers)

🇫🇷

Poitiers, France

Hospital General Unversitario Gregorio Marañón (Madrid)

🇪🇸

Madrid, Spain

CHU de Poitiers

🇫🇷

Poitiers, France

CHU de Rouen - Hôpital Charles-Nicolle

🇫🇷

Rouen, France

University of Southern California (USC) - Norris Cancer Hospital

🇺🇸

Los Angeles, California, United States

Stanford University and Lucile Packard Children's Hospital

🇺🇸

Palo Alto, California, United States

University of Florida Health Shands Children's Hospital

🇺🇸

Gainesville, Florida, United States

Levine Children's Hospital (LCH)

🇺🇸

Charlotte, North Carolina, United States

Cincinnati Children's Hospital Medical Center - Cancer and Blood Diseases Institute (CBDI)

🇺🇸

Cincinnati, Ohio, United States

MD Anderson Main Campus

🇺🇸

Houston, Texas, United States

Children's Hospital of the King's Daughters

🇺🇸

Norfolk, Virginia, United States

St. Anna Kinderspital Zentrum fuer Kinder- und Jugendheilkunde

🇦🇹

Vienna, Austria

Cliniques universitaires Saint-Luc

🇧🇪

Bruxelles, Belgium

University Hospital Gent

🇧🇪

Ghent, Belgium

Universitaire Ziekenhuizen Leuven

🇧🇪

Leuven, Belgium

Arthur J. E. Child Comprehensive Cancer Centre

🇨🇦

Calgary, Canada

McGill University Health Centre - Centre for Innovative Medicine

🇨🇦

Québec, Canada

Princess Margaret cancer center

🇨🇦

Toronto, Canada

Sinai Health System-Mount Sinai Hospital

🇨🇦

Toronto, Canada

Aarhus University Hospital

🇩🇰

Aarhus, Denmark

Copenhagen University Hospital - Rigshospitalet

🇩🇰

Kobenhavn, Denmark

Institut Bergonie

🇫🇷

Bordeaux, France

Centre Francois Baclesse

🇫🇷

Caen, France

Centre Oscar Lambret

🇫🇷

Lille, France

Centre Leon Berard

🇫🇷

Lyon, France

CHU de Nantes

🇫🇷

Nantes, France

CHRU de Strasbourg - Hopital de Hautepierre

🇫🇷

Strasbourg, France

Universitaetsklinikum Carl Gustav Carus Dresden

🇩🇪

Dresden, Germany

Universitätsklinikum Essen Westdeutsches Tumorzentrum Essen

🇩🇪

Essen, Germany

Klinikum Kassel Gesundheit Nordhessen

🇩🇪

Kassel, Germany

Universitaetsklinikum Köln - Kinderonkologie

🇩🇪

Köln, Germany

Universitätsmedizin Mainz

🇩🇪

Mainz, Germany

Klinikum rechts der Isar der Technischen Universitaet Muenchen

🇩🇪

Muenchen, Germany

Dr. von Haunerschen Kinderspital

🇩🇪

München, Germany

Medizinischen Klinik III - Onkologie und Hämatologie - am LMU Klinikum, München

🇩🇪

München, Germany

Olgahospital

🇩🇪

Stuttgart, Germany

St Vincent's University Hospital

🇮🇪

Dublin, Ireland

Ospedale Ortopedico Rizzoli di Bologna

🇮🇹

Bologna, Italy

Azienda Ospedaliero Universitaria Meyer

🇮🇹

Firenze, Italy

IRCCS Istituto Giannina Gaslini

🇮🇹

Genova, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

🇮🇹

Milano, Italy

Istituto Nazionale Tumor

🇮🇹

Naples, Italy

Azienda Ospedale - Università Padova

🇮🇹

Padova, Italy

AOU Città della Salute e della Scienza di Torino

🇮🇹

Piemonte, Italy

IRCCS - Istituto Nazionale Tumori Regina Elena

🇮🇹

Roma, Italy

Ospedale Paediatrico Bambino Gesù

🇮🇹

Roma, Italy

Azienda Ospedaliero-Universitaria Senese

🇮🇹

Siena, Italy

AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita

🇮🇹

Torino, Italy

Amsterdam UMC - Locatie AMC

🇳🇱

Amsterdam, Netherlands

Princess Maxima Center for paediatric oncology

🇳🇱

Utrecht, Netherlands

Instytut Matki i Dziecka

🇵🇱

Warsaw, Poland

Hospital de La Santa Creu i Sant Pau

🇪🇸

Barcelona, Spain

Hospital Sant Joan de Deu

🇪🇸

Barcelona, Spain

Hospital Universitario Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario La Paz

🇪🇸

La Paz, Spain

Hospital General Unversitario Gregorio Marañón

🇪🇸

Madrid, Spain

Hospital Infantil Universitario Nino Jesus

🇪🇸

Madrid, Spain

Hospital Universitario Son Espases

🇪🇸

Palma De Mallorca, Spain

Complejo Hospitalario Universitario de Santiago

🇪🇸

Santiago De Compostela, Spain

Hospital Universitario Virgen del Rocio

🇪🇸

Sevilla, Spain

Hospital Universitari i Politecnic La Fe

🇪🇸

Valencia, Spain

Birmingham Children's Hospital

🇬🇧

Birmingham, United Kingdom

Cambridge University Hospitals NHS Trust

🇬🇧

Cambridge, United Kingdom

NHS greater Glasgow and Clyde

🇬🇧

Glasgow, United Kingdom

University College London Hospital

🇬🇧

London, United Kingdom

Christie NHS Foundation Trust

🇬🇧

Manchester, United Kingdom

Royal Victoria Infirmary

🇬🇧

Newcastle Upon Tyne, United Kingdom

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