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

NCT06341712 | Terminated Phase 2 FDA Drug

• 2 other identifiers: CLIN-60000-4612023-506229-12-00
• Study Type: interventional
• Target: 10
• Locations: 10 countries
• Sites: 16

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.

Conditions

Osteosarcoma; Osteosarcoma in Children; Osteosarcoma in Adolescents and Young Adults

Keywords

Osteosarcoma; Cabozantinib; Children; Osteosarcoma in adolescents and young adults (AYA); AYA

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) assessed by Blinded Independent Radiology Committee (BIRC)

  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.

  From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months).

Secondary Outcomes (17)

• Progression-free survival (PFS) rate assessed by BIRC

  4 months and 1 year after randomization.

• Objective response rate (ORR) assessed by BIRC

  Approximately 34 months after randomization.

• Disease control rate (DCR) assessed by BIRC

  Approximately 34 months after randomization.

• PFS assessed by investigator

  From randomization until disease progression or death from any cause, whichever occurs first (approximately 34 months).

• PFS rate assessed by investigator

  At 4 months and 1 year after randomization.

Study Arms (2)

Arm A: Cabozantinib+ Best supportive care (BSC)

EXPERIMENTAL

Participants will receive cabozantinib and BSC.

Drug: Cabozantinib; Other: Best Supportive Care (BSC)

Arm B: Best supportive care (BSC)

OTHER

Participants will receive BSC alone administered per investigator's discretion and institutional guidelines.

Other: Best Supportive Care (BSC)

Interventions

Cabozantinib DRUG

Participants will receive cabozantinib orally Once daily (QD) on a continuous dosing schedule for cycles of 28 days.

Arm A: Cabozantinib+ Best supportive care (BSC)

Best Supportive Care (BSC) OTHER

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

Arm A: Cabozantinib+ Best supportive care (BSC)

Eligibility Criteria

• Age: 5 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ipsen: lead

Study Sites (16)

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507, United States

Location

University Hospital Gent

Ghent, Belgium

Location

McGill University Health Centre - Centre for Innovative Medicine

Québec, Canada

Location

Princess Margaret cancer center

Toronto, Canada

Location

Centre Oscar Lambret

Lille, France

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Dr. von Haunerschen Kinderspital

München, Germany

Location

Ospedale Ortopedico Rizzoli di Bologna

Bologna, Italy

Location

AOU Città della Salute e della Scienza di Torino

Piemonte, Italy

Location

Amsterdam UMC - Locatie AMC

Amsterdam, Netherlands

Location

Instytut Matki i Dziecka

Warsaw, Poland

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, Spain

Location

Hospital Infantil Universitario Nino Jesus

Madrid, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Spain

Location

Birmingham Children's Hospital

Birmingham, United Kingdom

Location

MeSH Terms

Conditions

Osteosarcoma

Interventions

cabozantinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

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 4, 2024
• First Posted: April 2, 2024
• Study Start: November 22, 2024
• Primary Completion: February 27, 2026
• Study Completion: February 27, 2026
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

ES (4); NL (1); FR (1); US (1); CA (2); GB (1); BE (1); IT (2); PL (1); DE (2)