Clinical trial NCT06341712: Effects of Maintenance Cabozantinib+BSC Versus BSC in Children and AYA With Osteosarcoma
Official title: A Phase II, Randomized, Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics (PK) of Maintenance Cabozantinib (XL184) Plus Best Supportive Care (BSC) Versus BSC in Children, Adolescents and Young Adults (AYA) With Unresectable Residual Osteosarcoma Either at Diagnosis or at First Relapse After Standard Treatment
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Osteosarcoma
Osteosarcoma in Children
Osteosarcoma in Adolescents and Young Adults
Keywords: Osteosarcoma
Cabozantinib
Children
Osteosarcoma in adolescents and young adults (AYA)
AYA
Lead sponsor: Ipsen
Sponsor class: INDUSTRY
First posted: 2024-04-02
Enrollment: 90
Sex: ALL
Minimum age (years): 5
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria :

* Participants must be ≥5 and ≤30 years of age at the time of study entry.
* Histologically or cytologically confirmed diagnosis of high-grade osteosarcoma as defined by a local pathologist
* Participants with unresectable residual disease after standard chemotherapy treatment at diagnosis or first relapse (treated with systemic chemotherapy). A minimum of 4 cycles of systemic chemotherapy (or minimum of 2 cycles if chemotherapy was stopped early due to toxicity) must have been received.
* Measurable residual or evaluable disease by RECIST version 1.1. Participants will be considered with evaluable disease if they have only non-measurable disease as per RECIST version 1.1 criteria.
* Absence of Progressive Disease (PD) (defined by the investigator according to RECIST version 1.1) at study entry. Note, the two most recent radiological evaluations (e.g. computerised tomography (CT) or magnetic resonance resonance imaging (MRI) scan) including the one following completion of chemotherapy should be available later to facilitate BIRC review.
* Chemotherapy must be the last anticancer treatment received by participants before study entry and must have been completed at least 4 weeks but no longer than 2 months before randomization.
* Participants must have recovered to Grade ≤1, except for alopecia, ototoxicity, and Grade ≤2 peripheral neuropathy, per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) from the acute toxic effects of all prior anticancer therapy at study entry, unless AEs are clinically non significant and/or stable on supportive therapy, per investigator clinical judgment.
* Life expectancy \>6 months.
* Performance level: participants must have a Lansky or Karnofsky performance status score of ≥70 corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0-1.
* Adequate organ and marrow function.
* Adequately controlled blood pressure (BP) with or without antihypertensive medications.
* Male and/or female (according to their reproductive organs and functions assigned by chromosomal complement) (FDA 2016)
* Contraception and barriers as well as pregnancy testing is required as appropriate for the age and sexual activity of pediatric participants and as required by local regulations.
* All participants (typically ≥18 years) and/or their parents or legal guardians must sign a written informed consent and assent must be obtained from minor participants according to local guidelines.

Exclusion Criteria :

* Low grade osteosarcoma and periosteal osteosarcoma
* Previous treatment with cabozantinib or another Mesenchymal-epithelial transition (MET)/hepatocyte growth factor (HGF) inhibitor (e.g., tivantinib, crizotinib).
* Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks or 5 half-lives of the agent, whichever is longer, before first dose of study intervention.
* Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study intervention (or washout of at least 5 half-lives, whichever is shorter).
* Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery or major surgery e.g., removal or biopsy of brain metastasis) and stable for at least 4 weeks prior to randomization. Eligible participants must be neurologically asymptomatic and without systemic corticosteroid treatment at the time of randomization. Note: Participants with a known seizure disorder who are receiving non-enzyme inducing anticonvulsants and have well-controlled seizures on a stable dose of anti-convulsant may be enrolled.
* Participants who have an uncontrolled/active infection requiring systemic therapy.
* Participants who are unable to swallow intact tablets.
* Participants with uncontrolled, significant intercurrent or recent illness.
* Previously identified allergy or hypersensitivity to components of the study treatment formulations.
* Any other active malignancy at time of first dose of study intervention or diagnosis of another malignancy within 3 years prior to first dose of study intervention that requires active treatment.
* Pregnancy or breast-feeding.
* Participants who in the opinion of the investigator may not be able to comply with the requirements of the study are not eligible
* Major surgery (eg, orthopaedic surgery, removal or biopsy of brain metastasis) within 8 weeks before randomization. Complete wound healing from major surgery must have occurred 4 weeks before randomization and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before randomization. Participants with clinically relevant ongoing complications from prior surgery are not eligible.

Primary outcomes:
measure: Progression-free Survival (PFS) assessed by Blinded Independent Radiology Committee (BIRC)
timeFrame: From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months).
Secondary outcomes:
measure: Progression-free survival (PFS) rate assessed by BIRC
timeFrame: 4 months and 1 year after randomization.
measure: Objective response rate (ORR) assessed by BIRC
timeFrame: Approximately 34 months after randomization.
measure: Disease control rate (DCR) assessed by BIRC
timeFrame: Approximately 34 months after randomization.
measure: PFS assessed by investigator
timeFrame: From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months).
measure: PFS rate assessed by investigator
timeFrame: At 4 months and 1 year after randomization.
measure: ORR assessed by investigator
timeFrame: Approximately 34 months after randomization.
measure: DCR assessed by investigator
timeFrame: Approximately 34 months after randomization.
measure: Overall survival (OS)
timeFrame: From randomization until death or last contact (approximately 34 months).
measure: 1-year overall survival rate
timeFrame: At 1 year after randomization.
measure: Percentage of participants with Treatment Emergent Adverse Event (TEAEs) and Adverse Events of Special Interest (AESIs).
timeFrame: From screening to 30 days after last dose.
measure: Area Under Curve (AUC) at steady state.
timeFrame: At Day 1 of week 1 and Day 1 of week 5.
measure: Average concentration (Cavg) at steady state
timeFrame: At Day 1 of week 1 and Day 1 of week 5.
measure: Minimum concentration (Cmin) at steady state
timeFrame: At Day 1 of week 1 and Day 1 of week 5.
measure: Maximal concentration (Cmax) at steady state
timeFrame: At Day 1 of week 1 and Day 1 of week 5.
measure: Acceptability and palatability in children and adolescents assessed using a horizontal visual assessment scale.
timeFrame: Day of first dose.
measure: Change from baseline in score for all Paediatric QoL Inventory (PedsQL) Scales including Generic Core Scales and Cancer Modules.
timeFrame: From screening to 30 days after last dose.
measure: Change from baseline in European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) (EORTC QLQ-C30) for adult participants
timeFrame: From screening to 30 days after last dose.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California (USC) - Norris Cancer Hospital
state: California
city: Palo Alto
country: United States
facility: Stanford University and Lucile Packard Children's Hospital
state: California
city: Gainesville
country: United States
facility: University of Florida Health Shands Children's Hospital
state: Florida
city: Charlotte
country: United States
facility: Levine Children's Hospital (LCH)
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center - Cancer and Blood Diseases Institute (CBDI)
state: Ohio
city: Houston
country: United States
facility: MD Anderson Main Campus
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Vienna
country: Austria
facility: St. Anna Kinderspital Zentrum fuer Kinder- und Jugendheilkunde
city: Bruxelles
country: Belgium
facility: Cliniques universitaires Saint-Luc
city: Ghent
country: Belgium
facility: University Hospital Gent
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven
city: Calgary
country: Canada
facility: Arthur J. E. Child Comprehensive Cancer Centre
city: Québec
country: Canada
facility: McGill University Health Centre - Centre for Innovative Medicine
city: Toronto
country: Canada
facility: Princess Margaret cancer center
city: Toronto
country: Canada
facility: Sinai Health System-Mount Sinai Hospital
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Kobenhavn
country: Denmark
facility: Copenhagen University Hospital - Rigshospitalet
city: Bordeaux
country: France
facility: Institut Bergonie
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Leon Berard
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: AP-HP Hopital Cochin
city: Paris
country: France
facility: Institut Curie
city: Poitiers
country: France
facility: CHU de Poitiers (Poitiers)
city: Poitiers
country: France
facility: CHU de Poitiers
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles-Nicolle
city: Strasbourg
country: France
facility: CHRU de Strasbourg - Hopital de Hautepierre
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital des Enfants
city: Villejuif
country: France
facility: Gustave Roussy
city: Berlin
country: Germany
facility: Charité - Kinderonkologie
city: Dortmund
country: Germany
facility: Klinikum Dortmund
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus Dresden
city: Essen
country: Germany
facility: Universitätsklinikum Essen Westdeutsches Tumorzentrum Essen
city: Kassel
country: Germany
facility: Klinikum Kassel Gesundheit Nordhessen
city: Köln
country: Germany
facility: Universitaetsklinikum Köln - Kinderonkologie
city: Mainz
country: Germany
facility: Universitätsmedizin Mainz
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der Technischen Universitaet Muenchen
city: München
country: Germany
facility: Dr. von Haunerschen Kinderspital
city: München
country: Germany
facility: Medizinischen Klinik III - Onkologie und Hämatologie - am LMU Klinikum, München
city: Stuttgart
country: Germany
facility: Olgahospital
city: Dublin
country: Ireland
facility: St Vincent's University Hospital
city: Bologna
country: Italy
facility: Ospedale Ortopedico Rizzoli di Bologna
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Meyer
city: Genova
country: Italy
facility: IRCCS Istituto Giannina Gaslini
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Naples
country: Italy
facility: Istituto Nazionale Tumor
city: Padova
country: Italy
facility: Azienda Ospedale - Università Padova
city: Piemonte
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
city: Roma
country: Italy
facility: IRCCS - Istituto Nazionale Tumori Regina Elena
city: Roma
country: Italy
facility: Ospedale Paediatrico Bambino Gesù
city: Siena
country: Italy
facility: Azienda Ospedaliero-Universitaria Senese
city: Torino
country: Italy
facility: AOU Citta della Salute e della Scienza di Torino - Ospedale Regina Margherita
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC
city: Utrecht
country: Netherlands
facility: Princess Maxima Center for paediatric oncology
city: Warsaw
country: Poland
facility: Instytut Matki i Dziecka
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: La Paz
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital General Unversitario Gregorio Marañón (Madrid)
city: Madrid
country: Spain
facility: Hospital General Unversitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Trust
city: Glasgow
country: United Kingdom
facility: NHS greater Glasgow and Clyde
city: London
country: United Kingdom
facility: University College London Hospital
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: Royal Victoria Infirmary
Study officials:
affiliation: Ipsen
name: Ipsen Medical Director
role: STUDY_DIRECTOR
References: