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

Conditions

• High Grade Osteosarcoma
• Localized Osteosarcoma
• Metastatic Osteosarcoma
• Secondary Osteosarcoma

Eligibility Criteria

Sex

ALL

Age

N/A - 40 Years

Healthy Volunteers

Not accepted

Interventions

• Bone Scan — PROCEDURE
  Undergo bone scintography
• Cabozantinib S-malate — DRUG
  Given PO
• Cisplatin — DRUG
  Given IV
• Computed Tomography — PROCEDURE
  Undergo CT
• Doxorubicin Hydrochloride — DRUG
  Given IV
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Methotrexate — DRUG
  Given IV
• Surgical Procedure — PROCEDURE
  Undergo surgery
• X-Ray Imaging — PROCEDURE
  Undergo X-ray

Study Details

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.

Key Dates

Start date

Mar 3, 2023

Status verified

Mar 2026

Primary completion

Mar 20, 2030

Completion

Mar 20, 2030

Study Design

Enrollment

1,122 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Active Comparator: Efficacy Phase Arm A (MAP)
  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.
• Experimental: Efficacy Phase Arm B (cabozantinib, MAP)
  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.
• Active Comparator: Efficacy Phase Arm C (MAP)
  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.
• Experimental: Efficacy Phase Arm D (cabozantinib, MAP)
  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.
• Experimental: Feasibility phase (cabozantinib, MAP)
  (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.

Primary Outcome Measure

Occurrence of dose-limiting toxicity (Feasibility) [ Time Frame: Baseline up to 6 weeks ]

Locations (175)

Find similar trials in Birmingham, AL

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