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Trial record 1 of 1 for:    nct00667342
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A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00667342
First received: April 24, 2008
Last updated: July 11, 2014
Last verified: June 2014
  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 Intervention Phase
Osteosarcoma
Malignant Fibrous Histiocytoma (MFH) of Bone
Biological: Bevacizumab
Drug: Cisplatin
Drug: Doxorubicin
Drug: Methotrexate
Drug: Ifosfamide
Drug: etoposide
Procedure: Surgery
Radiation: Radiotherapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of Bevacizumab, a Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor (VEGF), in Combination With Chemotherapy for Treatment of Osteosarcoma

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • Number of Participants With Unacceptable Toxicity [ Time Frame: After all patients have completed therapy, up to 1 year after last patient is enrolled ] [ Designated as safety issue: Yes ]

    Objective: To study the feasibility of combining: 1) bevacizumab with cisplatin, doxorubicin, and high-dose methotrexate (MAP) in patients with localized resectable osteosarcoma; and 2) bevacizumab with MAP and ifosfamide, and etoposide in patients with unresectable or metastatic osteosarcoma.

    The target unacceptable toxicity is defined as grade 4 hypertension, proteinuria, or bleeding excluding petechiae/purpura, grade 3/4 thrombosis/embolism excluding catheter-related thrombosis. The unacceptable toxicity for major wound complication is defined as grade 2, 3, or 4 major wound complications.

    A six-stage group sequential stopping rule was developed for monitoring unacceptable toxicity.


  • 3-Year Event Free Survival Compared to Historical Controls on the Intergroup Study 0133 [ Time Frame: After all patients have completed therapy, up to 4 years after last patient is enrolled ] [ 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.


Secondary Outcome Measures:
  • Histologic Response by Stratum [ Time Frame: After 6 cycles of chemotherapy, up to 1 year after the start of therapy ] [ Designated as safety issue: No ]

    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.

    Histologic response at week 10 of therapy was evaluated by Huvos grading systems as grade I: tumor not responding to therapy, no effect identified; grade IIA: more than 50% viable tumor left; grade IIB: 5-50% viable tumor remaining; grade III: only scattered foci of viable tumor seen (less than 5% of tumor); grade IV: no viable tumor seen in extensive sampling (at least a full cross-section of the tumor).

    The study did not enroll an adequate number of participants, therefore, the comparison to Intergroup Study 0133 participants was not done.


  • 2-Year Event Free Survival of Patients With Osteosarcoma [ Time Frame: After all patients have completed therapy, up to 3 years after last patient is enrolled ] [ Designated as safety issue: No ]
    To estimate the EFS and overall survival of patients with osteosarcoma treated with chemotherapy and bevacizumab.

  • 2-Year Overall Survival of Patients With Osteosarcoma [ Time Frame: After all patients have completed therapy, up to 3 years after last patient is enrolled ] [ Designated as safety issue: No ]
    To estimate the EFS and overall survival of patients with osteosarcoma treated with chemotherapy and bevacizumab.

  • 2-Year Event Free Survival in Patients With Localized Resectable Disease Compared to OS99 Protocol. [ Time Frame: After all patients have completed therapy, up to 3 years after last patient is enrolled ] [ 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.

  • 2-Year Overall Survival in Patients With Localized Resectable Disease Compared to OS99 Protocol. [ Time Frame: After all patients have completed therapy, up to 3 years after last patient is enrolled ] [ 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.


Enrollment: 43
Study Start Date: May 2008
Estimated Study Completion Date: April 2018
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: Bevacizumab
Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).
Other Names:
  • rhuMAb VEGF
  • Avastin®
Drug: Cisplatin
Given IV.
Other Name: Platinol-AQ®
Drug: Doxorubicin
Given IV.
Other Name: Adriamycin®
Drug: Methotrexate
Given IV.
Other Name: MTX
Procedure: Surgery
Participants undergo definitive surgery and assessment of histologic response at week 10.
Experimental: 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.
Biological: Bevacizumab
Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).
Other Names:
  • rhuMAb VEGF
  • Avastin®
Drug: Cisplatin
Given IV.
Other Name: Platinol-AQ®
Drug: Doxorubicin
Given IV.
Other Name: Adriamycin®
Drug: Methotrexate
Given IV.
Other Name: MTX
Drug: Ifosfamide
Given IV.
Other Name: Ifex®
Drug: etoposide
Given IV.
Other Names:
  • VP-16
  • Vepesid®
Procedure: Surgery
Participants undergo definitive surgery and assessment of histologic response at week 10.
Radiation: Radiotherapy
Radiation therapy delivered for positive margins or intralesional resections.
Experimental: 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.
Biological: Bevacizumab
Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).
Other Names:
  • rhuMAb VEGF
  • Avastin®
Drug: Cisplatin
Given IV.
Other Name: Platinol-AQ®
Drug: Doxorubicin
Given IV.
Other Name: Adriamycin®
Drug: Methotrexate
Given IV.
Other Name: MTX
Drug: Ifosfamide
Given IV.
Other Name: Ifex®
Drug: etoposide
Given IV.
Other Names:
  • VP-16
  • Vepesid®
Procedure: Surgery
Participants undergo definitive surgery and assessment of histologic response at week 10.
Radiation: Radiotherapy
Radiation therapy delivered for positive margins or intralesional resections.

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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00667342

Locations
United States, California
Rady Children's Hospital and Health Center
San Diego, California, United States, 92123
United States, Maryland
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
NCI/NIH - Pediatric Oncology Branch
Bethesda, Maryland, United States, 20892
United States, Tennessee
St Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
St. Jude Children's Research Hospital
Genentech, Inc.
Investigators
Principal Investigator: Fariba Navid, MD St. Jude Children's Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00667342     History of Changes
Other Study ID Numbers: OS2008, GENENTECH PHARM
Study First Received: April 24, 2008
Results First Received: June 9, 2014
Last Updated: July 11, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Histiocytoma
Histiocytoma, Benign Fibrous
Histiocytoma, Malignant Fibrous
Osteosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms, Fibrous Tissue
Sarcoma
Antibodies, Monoclonal
Bevacizumab
Cisplatin
Doxorubicin
Endothelial Growth Factors
Etoposide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on November 20, 2014