A Study to Test the Addition of the Drug Cabozantinib to Chemotherapy in Patients With Newly Diagnosed Osteosarcoma

NCT05691478 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2022-08567AOST2032U10CA180886
• Study Type: interventional
• Target: 1,122
• Locations: 4 countries
• Sites: 196

Brief Summary

This phase II/III trial tests the safety, side effects, and best dose of the drug cabozantinib in combination with standard chemotherapy, and to compare the effect of adding cabozantinib to standard chemotherapy alone in treating patients with newly diagnosed osteosarcoma. Cabozantinib is in a class of medications called kinase inhibitors which block protein signals affecting new blood vessel formation and the ability to activate growth signaling pathways. This may help slow the growth of tumor cells. The drugs used in standard chemotherapy for this trial are methotrexate, doxorubicin, and cisplatin (MAP). Methotrexate stops cells from making DNA and may kill tumor cells. It is a type of antimetabolite. Doxorubicin is in a class of medications called anthracyclines. It works by slowing or stopping the growth of tumor cells in the body. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Adding cabozantinib to standard chemotherapy may work better in treating newly diagnosed osteosarcoma.

Conditions

High Grade Osteosarcoma; Secondary Osteosarcoma; Localized Osteosarcoma; Metastatic Osteosarcoma

Outcome Measures

Primary Outcomes (4)

• Occurrence of dose-limiting toxicity (Feasibility)

  Only patients with high risk osteosarcoma who have a primary tumor considered resectable at the time of enrollment will be enrolled to this part of the trial. If a feasible dose cannot be established, the study committee will consult with Children's Oncology Group leadership and National Cancer Institute Cancer Therapy Evaluation Program regarding possible modifications of the regimen and subsequent protocol amendment.

  Baseline up to 6 weeks

• Event-free survival (EFS) (Phase II)

  The randomization and analysis will be stratified according to risk group. An assessment of the reduction in risk for EFS-event at the designated landmark time will be used to determine whether the trial continues to part 3. If the study proceeds to part 3, patients enrolled to part 2 of the trial will contribute to the primary analyses for part 3 of the study. If the interim criterion for continuation is not obtained, accrual will be closed with the conclusion that cabozantinib does not reduce sufficiently the risk for EFS-event for patients with newly-diagnosed osteosarcoma.

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• EFS (Phase III)

  Will consist of two randomized phase 3 sub-studies ('Phase 3'). One will be conducted in standard risk patients and one will be conducted in high risk patients.

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• Overall survival

  From randomization until death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

Secondary Outcomes (5)

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• Change in symptom burden and tolerability

  Up to 5 years after completion of study treatment

Other Outcomes (9)

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

• EFS

  From randomization until disease progression, relapse, diagnosis of a second malignant neoplasm, death or last contact, whichever occurs first, assessed up to 5 years after completion of study treatment

Study Arms (5)

Efficacy Phase Arm A (MAP)

ACTIVE COMPARATOR

Standard risk patients receive methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study.

Procedure: Bone Scan; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Doxorubicin Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Methotrexate; Procedure: Surgical Procedure; Procedure: X-Ray Imaging

Efficacy Phase Arm B (cabozantinib, MAP)

EXPERIMENTAL

Standard risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive one 35-day "consolidation" cycle with methotrexate IV, doxorubicin IV, and cisplatin IV, then a second 35-day "consolidation" cycle with cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV, followed by two additional 35-day "consolidation" cycles with cabozantinib PO, methotrexate IV, and doxorubicin IV. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study.

Procedure: Bone Scan; Drug: Cabozantinib S-malate; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Doxorubicin Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Methotrexate; Procedure: Surgical Procedure; Procedure: X-Ray Imaging

Efficacy Phase Arm C (MAP)

ACTIVE COMPARATOR

High risk patients receive methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day cycles and methotrexate IV and doxorubicin IV for two additional 35-day cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study.

Procedure: Bone Scan; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Doxorubicin Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Methotrexate; Procedure: Surgical Procedure; Procedure: X-Ray Imaging

Efficacy Phase Arm D (cabozantinib, MAP)

EXPERIMENTAL

High risk patients receive cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles, followed by appropriate local control. Patients then receive one 35-day "consolidation" cycle with methotrexate IV, doxorubicin IV, and cisplatin IV, then a second 35-day "consolidation" cycle with cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV, followed by two additional 35-day "consolidation" cycles with cabozantinib PO, methotrexate IV, and doxorubicin IV. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles. Patients also undergo X-ray, CT, MRI, and PET or bone scintigraphy at diagnosis and additional time points throughout the trial. All patients also undergo collection of blood samples during screening and on study.

Procedure: Bone Scan; Drug: Cabozantinib S-malate; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Doxorubicin Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Methotrexate; Procedure: X-Ray Imaging

Feasibility phase (cabozantinib, MAP)

EXPERIMENTAL

(CLOSED TO ACCRUAL 05/09/2025): Patients receive cabozantinib orally (PO), methotrexate intravenously (IV), doxorubicin IV, and cisplatin IV for two 35-day "induction" cycles. Patients are then considered for appropriate local control. Then they receive "consolidation" with methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, followed by cabozantinib PO, methotrexate IV, doxorubicin IV, and cisplatin IV for one 35-day cycle, and cabozantinib PO, methotrexate IV, and doxorubicin IV for two 35-day cycles. Patients then receive cabozantinib PO for six 28-day "maintenance" cycles.

Procedure: Bone Scan; Drug: Cabozantinib S-malate; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Doxorubicin Hydrochloride; Procedure: Magnetic Resonance Imaging; Drug: Methotrexate; Procedure: Surgical Procedure; Procedure: X-Ray Imaging

Interventions

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Surgical Procedure PROCEDURE

Undergo surgery

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Feasibility phase (cabozantinib, MAP)

Cabozantinib S-malate DRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL 184, XL-184, XL184

Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Bone Scan PROCEDURE

Undergo bone scintography

Also known as: Bone Scintigraphy

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Methotrexate DRUG

Given IV

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

X-Ray Imaging PROCEDURE

Undergo X-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

Efficacy Phase Arm A (MAP); Efficacy Phase Arm B (cabozantinib, MAP); Efficacy Phase Arm C (MAP); Efficacy Phase Arm D (cabozantinib, MAP); Feasibility phase (cabozantinib, MAP)

Eligibility Criteria

• Age: Up to 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be \< 40 years of age at the time of enrollment.
• Patients must have a body surface area of \>= 0.8 m\^2 at the time of enrollment.
• Patients must have histologic diagnosis (by institutional pathologist) of newly diagnosed high grade osteosarcoma. Primary tumors of all extremity and axial sites are eligible as long as diagnosis of high-grade osteosarcoma is established. Osteosarcoma as a second malignancy is eligible if no prior exposure to systemic chemotherapies.
• Feasibility Phase (NOTE: as of Amendment #2B, the feasibility phase has been completed) Patients must have metastatic disease and a resectable primary tumor. Designation of a primary tumor as resectable will be determined at the time of diagnosis by the institutional multidisciplinary team.
• For this study, metastatic disease is defined as one or more of the following:
• Lesions which are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a bone or body cavity with the primary tumor. Skip lesions in the same bone as the primary tumor do not constitute metastatic disease. Skip lesions in an adjacent bone are considered bone metastases.
• Lung metastases: defined as biopsy-proven metastasis or the presence of one or more pulmonary lesions \>= 5 mm, OR multiple pulmonary lesions \>= 3 mm or greater in size.
• Bone metastases: Areas suspicious for bone metastasis based on fludeoxyglucose F-18 (18F-FDG)-positron emission tomography (PET) scan (or whole body technetium-99 bone scan if 18F-FDG-PET is unavailable at the treating institution) require confirmatory biopsy or supportive anatomic imaging of at least one suspicious site with either magnetic resonance imaging (MRI) or computed tomography (CT) (whole body 18F-FDG-PET/CT or 18F-FDG-PET/MR scans are acceptable).
• Efficacy Phases (Phase 2/3) NOTE: as of Amendment #2B, the efficacy phase is open for enrollment.
• Patients with both localized and metastatic disease are eligible for the efficacy phase, regardless of resectability. Patients will be enrolled to two separate cohorts:
• Cohort 1 (Standard Risk): Patients with non-pelvic primary osteosarcoma deemed to be resectable at the time of diagnosis by the institutional multidisciplinary team, without evidence of metastatic lesions.
• Cohort 2 (High-Risk): Patients with a primary pelvic tumor, a primary tumor designated as unresectable by the institutional multidisciplinary team, AND/OR radiographic evidence of metastatic lesions.
• A serum creatinine based on age/sex as follows (within 7 days prior to enrollment unless otherwise indicated):
• (Age: Maximum Serum Creatinine \[mg/dL\]; Sex)
• month to \< 6 months: 0.4 (male); 0.4 (female)

You may not qualify if:

• Patients who have received previous systemic therapy for osteosarcoma or a prior oncologic diagnosis.
• Patients who have central nervous system metastases.
• Patients with central cavitating pulmonary lesions invading or encasing any major blood vessels in the lung.
• Patients who are unable to swallow tablets. Tablets cannot be crushed or chewed.
• Patients with gastrointestinal disorders including active disorders associated with a high risk of perforation or fistula formation. Specifically, no clinically significant gastrointestinal (GI) bleeding, GI perforation, bowel obstruction, intra-abdominal abscess or fistula for 6 months prior to enrollment, no hemoptysis or other signs of pulmonary hemorrhage for 3 months prior to enrollment.
• Patients with active bleeding or bleeding diathesis. No clinically significant hematuria, hematemesis, or hemoptysis or other history of significant bleeding within 3 months prior to enrollment.
• Patients with uncompensated or symptomatic hypothyroidism. Patients who have hypothyroidism controlled with thyroid replacement hormone are eligible.
• Patients with moderate to severe hepatic impairment (Child-Pugh B or C).
• Patients who have had primary tumor resection or attempted curative resection of metastases prior to enrollment.
• Patients who have undergone other major surgical procedure (eg, laparotomy) within 14 days prior to enrollment. Thoracoscopic procedures for diagnostic purposes (biopsy of lung nodule) and central access such as port-a-cath placement are allowed.
• Patients with any medical or surgical conditions that would interfere with gastrointestinal absorption of cabozantinib.
• Patients with previously identify allergy or hypersensitivity to components of the study treatment formulations.
• Patients who are receiving any other investigational agent not defined within this protocol are not eligible.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients who received enzyme-inducing anticonvulsants within 14 days prior to enrollment.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (196)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Banner Children's at Desert

Mesa, Arizona, 85202, United States

RECRUITING

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

RECRUITING

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

RECRUITING

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Mattel Children's Hospital UCLA

Los Angeles, California, 90095, United States

RECRUITING

Valley Children's Hospital

Madera, California, 93636, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Rady Children's Hospital - San Diego

San Diego, California, 92123, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, 80218, United States

RECRUITING

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

RECRUITING

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

RECRUITING

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

RECRUITING

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

RECRUITING

Miami Cancer Institute

Miami, Florida, 33176, United States

RECRUITING

AdventHealth Orlando

Orlando, Florida, 32803, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

Nemours Children's Hospital

Orlando, Florida, 32827, United States

RECRUITING

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States

RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Augusta University Medical Center

Augusta, Georgia, 30912, United States

RECRUITING

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

RECRUITING

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Illinois

Chicago, Illinois, 60612, United States

RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

OSF Children's Hospital of Illinois

Peoria, Illinois, 61637, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

Blank Children's Hospital

Des Moines, Iowa, 50309, United States

RECRUITING

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States

RECRUITING

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

RECRUITING

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

RECRUITING

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

RECRUITING

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889-5600, United States

RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655, United States

RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

RECRUITING

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan, 48183, United States

RECRUITING

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, 48038, United States

RECRUITING

Henry Ford Medical Center-Fairlane

Dearborn, Michigan, 48126, United States

RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Allegiance Health

Jackson, Michigan, 49201, United States

RECRUITING

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

RECRUITING

Henry Ford Medical Center-Columbus

Novi, Michigan, 48377, United States

RECRUITING

Corewell Health Children's

Royal Oak, Michigan, 48073, United States

RECRUITING

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

RECRUITING

Henry Ford Wyandotte Hospital

Wyandotte, Michigan, 48192, United States

RECRUITING

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

University of Missouri Children's Hospital

Columbia, Missouri, 65212, United States

RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

RECRUITING

Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

RECRUITING

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

RECRUITING

Summerlin Hospital Medical Center

Las Vegas, Nevada, 89144, United States

RECRUITING

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

RECRUITING

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

RECRUITING

Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

RECRUITING

Albany Medical Center

Albany, New York, 12208, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

RECRUITING

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

RECRUITING

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Stony Brook University Medical Center

Stony Brook, New York, 11794, United States

RECRUITING

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

RECRUITING

New York Medical College

Valhalla, New York, 10595, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

RECRUITING

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States

RECRUITING

Atrium Health Pineville/LCI-Pineville

Charlotte, North Carolina, 28210, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

RECRUITING

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

RECRUITING

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, 43606, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

RECRUITING

Penn State Children's Hospital

Hershey, Pennsylvania, 17033, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

RECRUITING

Saint Francis Hospital

Greenville, South Carolina, 29601, United States

RECRUITING

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

RECRUITING

Saint Francis Cancer Center

Greenville, South Carolina, 29607, United States

RECRUITING

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

RECRUITING

East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

RECRUITING

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

RECRUITING

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

El Paso Children's Hospital

El Paso, Texas, 79905, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Covenant Children's Hospital

Lubbock, Texas, 79410, United States

RECRUITING

UMC Cancer Center / UMC Health System

Lubbock, Texas, 79415, United States

RECRUITING

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

RECRUITING

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

RECRUITING

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

RECRUITING

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

RECRUITING

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405, United States

RECRUITING

Madigan Army Medical Center

Tacoma, Washington, 98431, United States

RECRUITING

West Virginia University Charleston Division

Charleston, West Virginia, 25304, United States

RECRUITING

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

RECRUITING

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States

RECRUITING

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

RECRUITING

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

RECRUITING

The Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

RECRUITING

Queensland Children's Hospital

South Brisbane, Queensland, 4101, Australia

RECRUITING

Monash Medical Center-Clayton Campus

Clayton, Victoria, 3168, Australia

RECRUITING

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

RECRUITING

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

RECRUITING

Children's Hospital

London, Ontario, N6A 5W9, Canada

RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, H3H 1P3, Canada

RECRUITING

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Centre Hospitalier Universitaire de Sherbrooke-Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

RECRUITING

Jim Pattison Children's Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

RECRUITING

CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

Québec, G1V 4G2, Canada

RECRUITING

Starship Children's Hospital

Grafton, Auckland, 1145, New Zealand

RECRUITING

Christchurch Hospital

Christchurch, 8011, New Zealand

RECRUITING

MeSH Terms

Conditions

Osteosarcoma

Interventions

cabozantinib; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Doxorubicin; Magnetic Resonance Spectroscopy; Methotrexate; merphos; Surgical Procedures, Operative; X-Rays; Phantoms, Imaging

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Michael W Bishop

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Single-arm Feasibility Phase study followed by a randomized, parallel 4-arm Efficacy Phase study

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: January 20, 2023
• Study Start: March 3, 2023
• Primary Completion (Estimated): March 20, 2030
• Study Completion (Estimated): March 20, 2030
• Last Updated: June 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (176); AU (6); NZ (2); CA (12)