Cabozantinib + Chemotherapy for Bone Cancer

Recruiting at 167 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticonvulsants, Anticoagulants, CYP3A4 drugs

Disqualifiers: CNS metastases, GI disorders, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 1

1122 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with newly diagnosed osteosarcoma, a type of bone cancer. Researchers aim to determine if adding the drug cabozantinib (Cabometyx) to standard chemotherapy can slow tumor growth more effectively than chemotherapy alone. The trial includes different treatment groups to compare results. It may suit those diagnosed with high-grade osteosarcoma who have not yet received treatment. As a Phase 3 trial, this research represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking advancements in osteosarcoma treatment.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are taking certain medications like strong CYP3A4 inducers or inhibitors, drugs that prolong QTc, or certain anticoagulants. It's best to discuss your current medications with the trial team to see if they are compatible with the study requirements.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cabozantinib has been studied for its safety in people with bone cancer. In one study, about 75% of patients taking cabozantinib experienced at least one side effect, indicating that side effects are common but generally manageable. Some serious side effects, like bleeding, can occur, though they are uncommon.

The FDA has already approved cabozantinib for other conditions, indicating a well-understood safety profile. However, it is not recommended for individuals with severe kidney problems due to unknown safety in this group.

In this trial, cabozantinib is combined with common chemotherapy drugs like methotrexate, doxorubicin, and cisplatin. These drugs have been extensively studied and used for a long time to treat cancer. They have known side effects, such as nausea and tiredness, which doctors can manage effectively.

Overall, while some risks exist, previous research indicates that cabozantinib is generally well-tolerated in patients. Always consult the medical team conducting the trial for detailed safety information and to determine if participation is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about cabozantinib in combination with chemotherapy for bone cancer because it introduces a novel approach to treatment. Unlike the standard chemotherapy treatments—methotrexate, doxorubicin, and cisplatin—cabozantinib works by targeting specific pathways that are involved in cancer growth and spread. This targeted mechanism could potentially enhance the effect of existing chemotherapy drugs, leading to better outcomes. Additionally, cabozantinib is administered orally, which can be more convenient for patients compared to intravenous treatments, offering a new level of comfort and flexibility in managing their condition.

What evidence suggests that this trial's treatments could be effective for osteosarcoma?

Studies have shown that cabozantinib can effectively treat osteosarcoma, a type of bone cancer. In patients with advanced stages of this cancer, cabozantinib demonstrated strong activity against tumors. Although no patients experienced a complete disappearance of the cancer, some managed to prevent disease progression for 1 to 8 months, with an average of 5 months. Cabozantinib blocks pathways that help cancer cells grow and form new blood vessels, potentially slowing tumor growth. In this trial, some participants will receive cabozantinib combined with standard chemotherapy treatments like methotrexate, doxorubicin, and cisplatin. This combination could potentially improve outcomes for those newly diagnosed with osteosarcoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Michael W Bishop

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for patients under 40 with newly diagnosed high-grade osteosarcoma, including those with localized or metastatic disease. They must have proper organ function and a body surface area of at least 0.8 m^2. HIV-positive patients are eligible if virally suppressed. Exclusions include pregnant women, those unable to swallow tablets, prior systemic therapy for osteosarcoma, certain heart conditions, uncontrolled hypertension, and recent major surgery.

Inclusion Criteria

You must be younger than 40 years old when you join the study.

All institutional, FDA, and NCI requirements for human studies must be met

HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible

Exclusion Criteria

Patients with active bleeding or bleeding diathesis

Patients with central cavitating pulmonary lesions invading or encasing any major blood vessels in the lung

Patients with uncompensated or symptomatic hypothyroidism

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive cabozantinib, methotrexate, doxorubicin, and cisplatin for two 35-day cycles

10 weeks

Multiple visits for drug administration

Consolidation

Patients receive methotrexate, doxorubicin, and cisplatin for one or two 35-day cycles, followed by additional cycles with cabozantinib

10-20 weeks

Multiple visits for drug administration

Maintenance

Patients receive cabozantinib for six 28-day cycles

24 weeks

Regular visits for monitoring and drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Periodic visits for imaging and blood sample collection

What Are the Treatments Tested in This Trial?

Interventions

• Cabozantinib
• Cisplatin
• Doxorubicin Hydrochloride
• Methotrexate

Trial Overview The study tests cabozantinib (a kinase inhibitor that may slow tumor growth) added to standard chemotherapy (methotrexate, doxorubicin hydrochloride, cisplatin) in treating new osteosarcoma cases. It's a phase II/III trial comparing the safety and effects of this combination against chemotherapy alone.

How Is the Trial Designed?

Group I: Feasibility phase (cabozantinib, MAP) Experimental Treatment 9 Interventions

(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.

Group II: Efficacy Phase Arm D (cabozantinib, MAP) Experimental Treatment 8 Interventions

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.

Group III: Efficacy Phase Arm B (cabozantinib, MAP) Experimental Treatment 9 Interventions

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.

Group IV: Efficacy Phase Arm A (MAP) Active Control 8 Interventions

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.

Group V: Efficacy Phase Arm C (MAP) Active Control 8 Interventions

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.

Cabozantinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in United States as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Canada as Cabometyx for:

• Renal cell carcinoma
• Hepatocellular carcinoma

Approved in Japan as Cabometyx for:

• Renal cell carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8763616/

Cabozantinib in Advanced Ewing Sarcomas and osteosarcomas In this study, cabozantinib showed marked antitumor activity in patients with advanced Ewing sarcoma and osteosarcoma and may represent a new ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.535

Evaluating the efficacy of cabozantinib in patients with ... Conclusions: Cabozantinib demonstrated favorable clinical effects on bone metastasis in patients with aRCC, as suggested by a high DCR. Our ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9918141/

Real-World Data on Cabozantinib in Advanced Osteosarcoma ... No objective response was noted, and 9/16 patients exhibited stable disease outcomes. Progression-free survival varied from 1 to 8 (median; 5) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05691478

NCT05691478 | A Study to Test the Addition of the Drug ... This phase II/III trial tests the safety, side effects, and best dose of the drug cabozantinib in combination with standard chemotherapy.

5. nature.com nature.com/articles/s41598-018-22469-5

Cabozantinib Affects Osteosarcoma Growth Through A ... The present study aimed to evaluate the effect of c-MET inhibitor cabozantinib (CBZ) on OS both directly and through its action on bone microenvironment.

6. cabometyx.com cabometyx.com/

CABOMETYX® (cabozantinib) Patient Website CABOMETYX may cause serious side effects, including: Bleeding (hemorrhage). CABOMETYX can cause severe bleeding that may lead to death.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/208692s012lbl.pdf

cabometyx - accessdata.fda.gov The safety of CABOMETYX was evaluated in COSMIC-311, a randomized, double-blind, placebo-controlled trial in which 187 patients with advanced differentiated ...

8. ema.europa.eu ema.europa.eu/en/documents/product-information/cabometyx-epar-product-information_en.pdf

Cabometyx, INN-Cabozantinib - EMA Cabozantinib is not recommended for use in patients with severe renal impairment as safety and efficacy have not been established in this population.