Trial record 1 of 1 for:    nct00667342
Previous Study | Return to List | Next Study

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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
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

April 24, 2008
July 11, 2014
May 2008
May 2014   (final data collection date for primary outcome measure)
  • 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.
  • Event Free Survival [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Feasibility [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00667342 on ClinicalTrials.gov Archive Site
  • 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.
Not Provided
Not Provided
Not Provided
 
A Study of Bevacizumab in Combination With Chemotherapy for Treatment of Osteosarcoma
A Study of Bevacizumab, a Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor (VEGF), in Combination With Chemotherapy for Treatment of Osteosarcoma

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Osteosarcoma
  • Malignant Fibrous Histiocytoma (MFH) of Bone
  • 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: 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.
    Interventions:
    • Biological: Bevacizumab
    • Drug: Cisplatin
    • Drug: Doxorubicin
    • Drug: Methotrexate
    • Procedure: Surgery
  • 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.
    Interventions:
    • Biological: Bevacizumab
    • Drug: Cisplatin
    • Drug: Doxorubicin
    • Drug: Methotrexate
    • Drug: Ifosfamide
    • Drug: etoposide
    • Procedure: Surgery
    • Radiation: Radiotherapy
  • 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.
    Interventions:
    • Biological: Bevacizumab
    • Drug: Cisplatin
    • Drug: Doxorubicin
    • Drug: Methotrexate
    • Drug: Ifosfamide
    • Drug: etoposide
    • Procedure: Surgery
    • Radiation: Radiotherapy
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
43
April 2018
May 2014   (final data collection date for primary outcome measure)

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
Both
up to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00667342
OS2008, GENENTECH PHARM
Yes
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Genentech
Principal Investigator: Fariba Navid, MD St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP