A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma

St. Jude Children's Research Hospital

Status and phase

Completed

Phase 2

Conditions

Osteosarcoma

Malignant Fibrous Histiocytoma (MFH) of Bone

Treatments

Radiation: Radiotherapy

Drug: Ifosfamide

Drug: Cisplatin

Drug: etoposide

Biological: Bevacizumab

Drug: Methotrexate

Procedure: Surgery

Drug: Doxorubicin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00667342

GENENTECH PHARM (Other Identifier)

NCI-2009-00846 (Registry Identifier)

OS2008

Details and patient eligibility

About

This study adopts a novel strategy for first-line treatment of osteosarcoma by combining chemotherapy with anti-angiogenic therapy using bevacizumab (Avastin®), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF). Chemotherapy for localized disease comprises a 3-drug regimen (cisplatin, doxorubicin, and high-dose methotrexate). Chemotherapy for metastatic or unresectable disease comprises a cisplatin-based regimen that includes high-dose methotrexate, doxorubicin, ifosfamide, and etoposide.

Full description

This is a comprehensive study that uses a novel agent that targets angiogenesis (bevacizumab) in combination with conventional chemotherapy for the treatment of osteosarcoma. Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor (VEGF), has been shown to stop the growth of new blood vessels of tumors, both in the laboratory and in patients with other types of cancers. Bevacizumab has improved the effect of chemotherapy in adult patients with different types of cancer by increasing tumor response and increasing the chances of survival. This study has two main goals:

To find out if bevacizumab can be combined safely with chemotherapy for osteosarcoma
To find out if adding bevacizumab to chemotherapy will be beneficial in treating osteosarcoma.

The chemotherapy drugs used in this study are commonly used to treat osteosarcoma. Patients with non-metastatic and resectable tumors receive bevacizumab and chemotherapy comprised of cisplatin, doxorubicin and high-dose methotrexate. Patients with metastatic tumors or tumors that cannot be removed by surgery receive bevacizumab and chemotherapy comprised of cisplatin, doxorubicin and high-dose methotrexate, ifosfamide and etoposide. If the tumor can be removed by surgery, surgery will be performed after 10 weeks of chemotherapy and will be followed by additional chemotherapy. After completion of active therapy, patient's response to therapy will be followed for approximately 5 years.

Enrollment

43 patients

Sex

All

Ages

Under 30 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patient must have newly diagnosed high-grade, biopsy proven, osteosarcoma or malignant fibrous histiocytoma (MFH) of bone with no history of prior chemotherapy or radiation;
Participant is able to perform tasks and daily activities as defined in the study guidelines
Patient meets established guidelines for adequate function of the kidney, liver, heart and bone marrow
Participants meets other requirements defined in the eligibility portion of the study

Exclusion criteria

recent major surgical procedure or injury
Known bleeding diathesis, platelet disorder or coagulopathy
Thrombosis
Cardiac disease or hypertension
Significant proteinuria
Central nervous system disease
Gastrointestinal perforation/abdominal fistula
Osteosarcoma or MFH of bone as second malignancy

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

43 participants in 3 patient groups

Localized Resectable Disease (Stratum A)

Experimental group

Description:

Participants with localized resectable disease receive Cycle 1 of bevacizumab 3 days before chemotherapy with cisplatin and doxorubicin. Subsequent cycles consist of bevacizumab on the first day of chemotherapy, then cisplatin, and doxorubicin, or methotrexate. If applicable, definitive surgery and assessment of histologic response will occur at week 10 followed by bevacizumab on the first day of chemotherapy with cisplatin and doxorubicin, or methotrexate.

Treatment:

Drug: Doxorubicin

Drug: Methotrexate

Biological: Bevacizumab

Procedure: Surgery

Drug: Cisplatin

Metastatic Disease (Stratum B)

Experimental group

Description:

Participants with metastatic disease (Stratum B) receive Cycle 1 of bevacizumab 3 days before chemotherapy with cisplatin and doxorubicin. Subsequent cycles consist of bevacizumab on the first day of chemotherapy, then cisplatin and doxorubicin, methotrexate or ifosfamide, and etoposide. If applicable, definitive surgery and assessment of histologic response will occur at week 10 followed by bevacizumab on the first day of chemotherapy with cisplatin and doxorubicin, methotrexate, or ifosfamide, and etoposide. Radiotherapy will be given post-operatively.

Treatment:

Drug: Doxorubicin

Drug: Methotrexate

Biological: Bevacizumab

Procedure: Surgery

Drug: etoposide

Drug: Cisplatin

Drug: Ifosfamide

Radiation: Radiotherapy

Unresectable Disease (Stratum C)

Experimental group

Description:

Participants with unresectable disease (Stratum C) receive treatment identical to Stratum B: Cycle 1 of bevacizumab 3 days before chemotherapy with cisplatin and doxorubicin. Subsequent cycles consist of bevacizumab on the first day of chemotherapy, then cisplatin and doxorubicin, methotrexate or ifosfamide, and etoposide. If applicable, definitive surgery and assessment of histologic response will occur at week 10 followed by bevacizumab on the first day of chemotherapy with cisplatin and doxorubicin, methotrexate, or ifosfamide, and etoposide. Radiotherapy will be given post-operatively.

Treatment:

Drug: Doxorubicin

Drug: Methotrexate

Biological: Bevacizumab

Procedure: Surgery

Drug: etoposide

Drug: Cisplatin

Drug: Ifosfamide

Radiation: Radiotherapy