Clinical trial NCT00667342: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteosarcoma
Malignant Fibrous Histiocytoma (MFH) of Bone
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-04-28
Enrollment: 43
Sex: ALL
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Unacceptable Toxicity
timeFrame: After all patients have completed therapy, up to 1 year after last patient is enrolled
measure: 3-Year Event Free Survival
timeFrame: After all patients have completed therapy, up to 4 years after last patient is enrolled
Secondary outcomes:
measure: Histologic Response by Stratum
timeFrame: After 6 cycles of chemotherapy, up to 1 year after the start of therapy
measure: 2-Year Event Free Survival (EFS) of Patients With Osteosarcoma
timeFrame: After all patients have completed therapy, up to 2 years after last patient is enrolled
measure: 2-Year Overall Survival (OS) of Patients With Osteosarcoma
timeFrame: After all patients have completed therapy, up to 2 years after last patient is enrolled
measure: 2-Year Event Free Survival (EFS) in Patients With Localized Resectable Disease Compared to St. Jude OS99 Protocol.
timeFrame: After all patients have completed therapy, up to 2 years after last patient is enrolled
measure: 2-Year Overall Survival (OS) in Patients With Localized Resectable Disease Compared to OS99 Protocol.
timeFrame: After all patients have completed therapy, up to 2 years after last patient is enrolled
measure: Mean Ktrans
timeFrame: Baseline through Week 10
measure: Mean Vp
timeFrame: Baseline through Week 10
measure: Mean Ve
timeFrame: Baseline through Week 10
measure: Histologic Response by Number of Participants
timeFrame: at week 10 after start of therapy
measure: Ktrans by Good and Poor Response
timeFrame: at week 10 after start of therapy
measure: P95 of Ktrans by Good and Poor Response
timeFrame: at week 10 after start of therapy
measure: Difference Between Good and Poor Response by SUVmax
timeFrame: at week 10 after start of therapy
Other outcomes:
measure: Number of Participants With Neuropathic Pain (NP) Following Surgery
timeFrame: Up to 6 months postoperatively
measure: Median Duration of Neuropathic Pain
timeFrame: From surgery until resolution of NP symptoms, up to 6 months
measure: Mean Duration of Neuropathic Pain
timeFrame: From surgery until resolution of NP symptoms, up to 6 months
measure: Median Duration of Neuropathic Pain Medication
timeFrame: From surgery until resolution of NP symptoms, up to 6 months
measure: Mean Duration of Neuropathic Pain Medication
timeFrame: From surgery until resolution of NP symptoms, up to 6 months
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital and Health Center
state: California
city: Baltimore
country: United States
facility: Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
state: Maryland
city: Bethesda
country: United States
facility: NCI/NIH - Pediatric Oncology Branch
state: Maryland
city: Memphis
country: United States
facility: St Jude Children's Research Hospital
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Michael Bishop, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.