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

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

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Osteosarcoma Malignant Fibrous Histiocytoma (MFH) of Bone
Intervention	Biological: Bevacizumab Drug: Chemotherapy (Cisplatin, Doxorubicin, Methotrexate, Ifosfamide, Etoposide)
Phase	Phase 2
Sponsor	St. Jude Children's Research Hospital
Responsible Party	St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier	NCT00667342
First Received	April 24, 2008
Last Updated	July 30, 2013
Last verified	July 2013

Tracking Information[ + expand ][ + ]

First Received Date	April 24, 2008
Last Updated Date	July 30, 2013
Start Date	May 2008
Estimated Primary Completion Date	April 2018
Current Primary Outcome Measures	Feasibility [Time Frame: 5 years] [Designated as safety issue: Yes]To study the feasibility of combining bevacizumab (Avastin®), a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), with cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) in patients with localized resectable osteosarcoma, and bevacizumab with cisplatin, doxorubicin, HDMTX, ifosfamide, and etoposide in patients with unresectable or metastatic osteosarcoma. Event Free Survival compared to historical controls on the Intergroup Study 0133 [Time Frame: 7 years] [Designated as safety issue: No]To study the effect of adding bevacizumab to chemotherapy comprised of cisplatin, doxorubicin, and HDMTX on the event-free survival (EFS) in patients with localized resectable osteosarcoma compared to historical controls treated with cisplatin, doxorubicin, and HDMTX without bevacizumab on the Intergroup Study 0133.
Current Secondary Outcome Measures	Histologic response in patients with localized resectable osteosarcoma compared to Intergroup Study 0133 patients [Time Frame: 5 years plus 6 cycles of chemotherapy] [Designated as safety issue: No]To study the effect of adding bevacizumab to preoperative chemotherapy comprised of cisplatin, doxorubicin, and HDMTX on the histologic response in patients with localized resectable osteosarcoma compared to historical controls treated with preoperative cisplatin, doxorubicin, and HDMTX without bevacizumab on the Intergroup Study 0133. Event free survival of patients with osteosarcoma [Time Frame: 6 years] [Designated as safety issue: No]To estimate the EFS and overall survival of patients with osteosarcoma treated with chemotherapy and bevacizumab. Overall survival of patients with osteosarcoma [Time Frame: 6 years] [Designated as safety issue: No]To estimate the EFS and overall survival of patients with osteosarcoma treated with chemotherapy and bevacizumab. Event free survival in patients with localized resectable disease compared to OS99 protocol. [Time Frame: 6 years] [Designated as safety issue: No]To compare outcomes (EFS and survival) of patients with localized resectable disease treated on this protocol vs. those treated on the OS99 protocol. Overall survival in patients with localized resectable disease compared to OS99 protocol. [Time Frame: 6 years] [Designated as safety issue: No]To compare outcomes (EFS and survival) of patients with localized resectable disease treated on this protocol vs. those treated on the OS99 protocol.

Descriptive Information[ + expand ][ + ]

Brief Title	A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma
Official Title	A Study of Bevacizumab, a Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor (VEGF), in Combination With Chemotherapy for Treatment of Osteosarcoma
Brief Summary	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.
Detailed 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.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Osteosarcoma Malignant Fibrous Histiocytoma (MFH) of Bone
Intervention	Biological: Bevacizumab Monoclonal Antibody against VEGF Drug: Chemotherapy (Cisplatin, Doxorubicin, Methotrexate, Ifosfamide, Etoposide) Cisplatin, Doxorubicin, Methotrexate, Ifosfamide, Etoposide. Participants with resectable localized disease (Stratum A) only receive cisplatin, methotrexate and doxorubicin.
Study Arm (s)	Experimental: 1 See intervention description.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Active, not recruiting
Estimated Enrollment	95
Estimated Completion Date	April 2018
Estimated Primary Completion Date	May 2014
Eligibility Criteria	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
Gender	Both
Ages	N/A
Accepts Healthy Volunteers	No
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT00667342
Other Study ID Numbers	OS2008
Has Data Monitoring Committee	Yes
Information Provided By	St. Jude Children's Research Hospital
Study Sponsor	St. Jude Children's Research Hospital
Collaborators	Genentech
Investigators	Principal Investigator: Fariba Navid, MD St. Jude Children's Research Hospital
Verification Date	July 2013

Locations[ + expand ][ + ]

Rady Children's Hospital and Health Center	San Diego, California, United States, 92123
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center	Baltimore, Maryland, United States, 21231
NCI/NIH - Pediatric Oncology Branch	Bethesda, Maryland, United States, 20892
St Jude Children's Research Hospital	Memphis, Tennessee, United States, 38105
MD Anderson Cancer Center	Houston, Texas, United States, 77030-4009