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

Primary Purpose

Osteosarcoma, Malignant Fibrous Histiocytoma (MFH) of Bone

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Cisplatin
Doxorubicin
Methotrexate
Ifosfamide
etoposide
Surgery
Radiotherapy
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteosarcoma

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

  • Rady Children's Hospital and Health Center
  • Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
  • NCI/NIH - Pediatric Oncology Branch
  • St Jude Children's Research Hospital
  • MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Localized Resectable Disease (Stratum A)

Metastatic Disease (Stratum B)

Unresectable Disease (Stratum C)

Arm 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.

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.

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.

Outcomes

Primary Outcome Measures

Number of Participants With Unacceptable Toxicity
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
To study the effect of adding bevacizumab to chemotherapy comprised of cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) on the event-free survival (EFS) in patients with localized resectable osteosarcoma. The Kaplan-Meier (K-M) method was used to estimate survival rate.

Secondary Outcome Measures

Histologic Response by Stratum
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 (EFS) of Patients With Osteosarcoma
Kaplan-Meier method was used to estimate the EFS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.
2-Year Overall Survival (OS) of Patients With Osteosarcoma
Kaplan-Meier method was used to estimate the OS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.
2-Year Event Free Survival (EFS) in Patients With Localized Resectable Disease Compared to St. Jude OS99 Protocol.
The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS20008 to that of OS99 (NCT00145639) participants was not done. The 2-year EFS of OS2008 participants is reported here.
2-Year Overall Survival (OS) in Patients With Localized Resectable Disease Compared to OS99 Protocol.
The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS2008 to that of OS99 (NCT00145639) participants was not done. The 2-year OS of OS2008 participants is reported here.
Mean Ktrans
The volume transfer constant (Ktrans) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Mean Vp
The fractional blood plasma volume (Vp) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Mean Ve
The fractional volume of extravascular extracellular space (Ve) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Histologic Response by Number of Participants
The association of interested variables with response was checked with the Wilcoxon rank-sum test. The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Ktrans by Good and Poor Response
The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
P95 of Ktrans by Good and Poor Response
The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%. P95 denotes the level of each kinetic parameter exceeding 95% of its values in each tumor.
Difference Between Good and Poor Response by SUVmax
The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.

Full Information

First Posted
April 24, 2008
Last Updated
August 3, 2023
Sponsor
St. Jude Children's Research Hospital
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00667342
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
June 3, 2008 (Actual)
Primary Completion Date
August 2014 (Actual)
Study Completion Date
August 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
St. Jude Children's Research Hospital
Collaborators
Genentech, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma, Malignant Fibrous Histiocytoma (MFH) of Bone

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Localized Resectable Disease (Stratum A)
Arm Type
Experimental
Arm 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.
Arm Title
Metastatic Disease (Stratum B)
Arm Type
Experimental
Arm 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.
Arm Title
Unresectable Disease (Stratum C)
Arm Type
Experimental
Arm 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.
Intervention Type
Biological
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
rhuMAb VEGF, Avastin®
Intervention Description
Monoclonal Antibody against vascular endothelial growth factor (VEGF). Given intravenously (IV).
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
Platinol-AQ®
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin®
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
MTX
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
Ifosfamide
Other Intervention Name(s)
Ifex®
Intervention Description
Given IV.
Intervention Type
Drug
Intervention Name(s)
etoposide
Other Intervention Name(s)
VP-16, Vepesid®
Intervention Description
Given IV.
Intervention Type
Procedure
Intervention Name(s)
Surgery
Intervention Description
Participants undergo definitive surgery and assessment of histologic response at week 10.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Radiation therapy delivered for positive margins or intralesional resections.
Primary Outcome Measure Information:
Title
Number of Participants With Unacceptable Toxicity
Description
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.
Time Frame
After all patients have completed therapy, up to 1 year after last patient is enrolled
Title
3-Year Event Free Survival
Description
To study the effect of adding bevacizumab to chemotherapy comprised of cisplatin, doxorubicin, and high-dose methotrexate (HDMTX) on the event-free survival (EFS) in patients with localized resectable osteosarcoma. The Kaplan-Meier (K-M) method was used to estimate survival rate.
Time Frame
After all patients have completed therapy, up to 4 years after last patient is enrolled
Secondary Outcome Measure Information:
Title
Histologic Response by Stratum
Description
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.
Time Frame
After 6 cycles of chemotherapy, up to 1 year after the start of therapy
Title
2-Year Event Free Survival (EFS) of Patients With Osteosarcoma
Description
Kaplan-Meier method was used to estimate the EFS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.
Time Frame
After all patients have completed therapy, up to 2 years after last patient is enrolled
Title
2-Year Overall Survival (OS) of Patients With Osteosarcoma
Description
Kaplan-Meier method was used to estimate the OS of patients with osteosarcoma treated with chemotherapy and Bevacizumab.
Time Frame
After all patients have completed therapy, up to 2 years after last patient is enrolled
Title
2-Year Event Free Survival (EFS) in Patients With Localized Resectable Disease Compared to St. Jude OS99 Protocol.
Description
The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS20008 to that of OS99 (NCT00145639) participants was not done. The 2-year EFS of OS2008 participants is reported here.
Time Frame
After all patients have completed therapy, up to 2 years after last patient is enrolled
Title
2-Year Overall Survival (OS) in Patients With Localized Resectable Disease Compared to OS99 Protocol.
Description
The current protocol OS2008 (NCT00667342) was closed early due to slow accrual. Thus, with the limited number of patients, the comparison of EFS of OS2008 to that of OS99 (NCT00145639) participants was not done. The 2-year OS of OS2008 participants is reported here.
Time Frame
After all patients have completed therapy, up to 2 years after last patient is enrolled
Title
Mean Ktrans
Description
The volume transfer constant (Ktrans) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Time Frame
Baseline through Week 10
Title
Mean Vp
Description
The fractional blood plasma volume (Vp) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Time Frame
Baseline through Week 10
Title
Mean Ve
Description
The fractional volume of extravascular extracellular space (Ve) was used to evaluate clinical outcomes. The average for the distribution across the whole region of interest (ROI) was calculated as a summary measure for each data set.
Time Frame
Baseline through Week 10
Title
Histologic Response by Number of Participants
Description
The association of interested variables with response was checked with the Wilcoxon rank-sum test. The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Time Frame
at week 10 after start of therapy
Title
Ktrans by Good and Poor Response
Description
The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Time Frame
at week 10 after start of therapy
Title
P95 of Ktrans by Good and Poor Response
Description
The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%. P95 denotes the level of each kinetic parameter exceeding 95% of its values in each tumor.
Time Frame
at week 10 after start of therapy
Title
Difference Between Good and Poor Response by SUVmax
Description
The response is based on the Huvos grade of histologic response for DCE-MRI comparisons and is defined as good for ≥90% necrosis and poor for less than 90%.
Time Frame
at week 10 after start of therapy
Other Pre-specified Outcome Measures:
Title
Number of Participants With Neuropathic Pain (NP) Following Surgery
Description
Of the 43 participants enrolled on this trial, 37 met criteria for evaluation of neuropathic pain (NP) following definitive surgery. The 37 participants underwent 38 surgeries: one participant had a limb-sparing surgery followed by an amputation surgery. Six of 43 participants were excluded from evaluation for NP: 1 due to deep vein thrombosis, 2 removed from study prior to surgery, 1 removed immediately after surgery to receive radiation therapy, 1 had non-extremity osteosarcoma, and 1 patient had a fibula resection. Patients were followed for neuropathic pain daily for the first week postoperatively and weekly for up to 6 months postoperatively.
Time Frame
Up to 6 months postoperatively
Title
Median Duration of Neuropathic Pain
Description
Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain. Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame
From surgery until resolution of NP symptoms, up to 6 months
Title
Mean Duration of Neuropathic Pain
Description
Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain (NP). Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame
From surgery until resolution of NP symptoms, up to 6 months
Title
Median Duration of Neuropathic Pain Medication
Description
Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain (NP). Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame
From surgery until resolution of NP symptoms, up to 6 months
Title
Mean Duration of Neuropathic Pain Medication
Description
Thirty participants who underwent surgery (31 surgeries) were determined to have neuropathic pain. Four participants received only opioids for NP and 26 participants (for 27 surgeries) were treated with NP specific medications including gabapentin, tricyclic antidepressant, methadone. One participant had 2 different surgical procedures and was analyzed both in the limb sparing group and in the amputation group.
Time Frame
From surgery until resolution of NP symptoms, up to 6 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Bishop, MD
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rady Children's Hospital and Health Center
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
NCI/NIH - Pediatric Oncology Branch
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
Facility Name
St Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24637635
Citation
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.
Results Reference
derived
Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital
URL
http://www.stjude.org/protocols
Description
Clinical Trials Open at St. Jude

Learn more about this trial

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

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