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

NCT ID: NCT00667342

Last Updated: 2023-08-07

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

43 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-03

Study Completion Date

2017-08-31

Brief Summary

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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

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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.

Conditions

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Osteosarcoma Malignant Fibrous Histiocytoma (MFH) of Bone

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Localized Resectable Disease (Stratum A)

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).

Cisplatin

Intervention Type DRUG

Given IV.

Doxorubicin

Intervention Type DRUG

Given IV.

Methotrexate

Intervention Type DRUG

Given IV.

Surgery

Intervention Type PROCEDURE

Participants undergo definitive surgery and assessment of histologic response at week 10.

Metastatic Disease (Stratum B)

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).

Cisplatin

Intervention Type DRUG

Given IV.

Doxorubicin

Intervention Type DRUG

Given IV.

Methotrexate

Intervention Type DRUG

Given IV.

Ifosfamide

Intervention Type DRUG

Given IV.

etoposide

Intervention Type DRUG

Given IV.

Surgery

Intervention Type PROCEDURE

Participants undergo definitive surgery and assessment of histologic response at week 10.

Radiotherapy

Intervention Type RADIATION

Radiation therapy delivered for positive margins or intralesional resections.

Unresectable Disease (Stratum C)

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.

Group Type EXPERIMENTAL

Bevacizumab

Intervention Type BIOLOGICAL

Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).

Cisplatin

Intervention Type DRUG

Given IV.

Doxorubicin

Intervention Type DRUG

Given IV.

Methotrexate

Intervention Type DRUG

Given IV.

Ifosfamide

Intervention Type DRUG

Given IV.

etoposide

Intervention Type DRUG

Given IV.

Surgery

Intervention Type PROCEDURE

Participants undergo definitive surgery and assessment of histologic response at week 10.

Radiotherapy

Intervention Type RADIATION

Radiation therapy delivered for positive margins or intralesional resections.

Interventions

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Bevacizumab

Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).

Intervention Type BIOLOGICAL

Cisplatin

Given IV.

Intervention Type DRUG

Doxorubicin

Given IV.

Intervention Type DRUG

Methotrexate

Given IV.

Intervention Type DRUG

Ifosfamide

Given IV.

Intervention Type DRUG

etoposide

Given IV.

Intervention Type DRUG

Surgery

Participants undergo definitive surgery and assessment of histologic response at week 10.

Intervention Type PROCEDURE

Radiotherapy

Radiation therapy delivered for positive margins or intralesional resections.

Intervention Type RADIATION

Other Intervention Names

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rhuMAb VEGF Avastin® Platinol-AQ® Adriamycin® MTX Ifex® VP-16 Vepesid®

Eligibility Criteria

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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
Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Bishop, MD

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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Rady Children's Hospital and Health Center

San Diego, California, United States

Site Status

Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

NCI/NIH - Pediatric Oncology Branch

Bethesda, Maryland, United States

Site Status

St Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

References

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Turner DC, Navid F, Daw NC, Mao S, Wu J, Santana VM, Neel M, Rao B, Willert JR, Loeb DM, Harstead KE, Throm SL, Freeman BB 3rd, Stewart CF. Population pharmacokinetics of bevacizumab in children with osteosarcoma: implications for dosing. Clin Cancer Res. 2014 May 15;20(10):2783-92. doi: 10.1158/1078-0432.CCR-13-2364. Epub 2014 Mar 17.

Reference Type DERIVED
PMID: 24637635 (View on PubMed)

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

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GENENTECH PHARM

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2009-00846

Identifier Type: REGISTRY

Identifier Source: secondary_id

OS2008

Identifier Type: -

Identifier Source: org_study_id

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