Timing of Surgery in Nonmetastatic Osteosarcoma of the Pelvis and Sacrum

Study Overview
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Brief Summary
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To study the effect of the timing of surgery on outcome of patients with nonmetastatic osteosarcoma of pelvis and sacrum.

Detailed Description
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Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma of pelvis and sacrum have included surgery with adjuvant chemotherapy. Pre-surgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of pre-surgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy, especially in the axial region. The contribution of chemotherapy and surgery timing has not been tested rigorously. To study the effect of the timing of surgery on outcome of patients with nonmetastatic osteosarcoma of pelvis and sacrum, we conducted multicenter randomized trial to determine whether chemotherapy administered before definitive resection of primary tumors improved EFS and overall survival compared with traditional resection of the primary tumor followed by adjuvant chemotherapy.

Official Title
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Presurgical Chemotherapy Compared With Immediate Surgery and Adjuvant Chemotherapy for Nonmetastatic Osteosarcoma of the Pelvis and Sacrum

Conditions
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Osteosarcoma of Pelvis

Intervention / Treatment
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* Drug: Doxorubicin
* Drug: Cisplatin
* Drug: Methotrexate
* Drug: Ifosfamide
* Procedure: definitive surgery
* Other: pre surgical chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >10 years and <40 years; High-grade nonmetastatic osteosarcoma in pelvis or sacrum; Diagnosis confirmed histologically and reviewed centrally; No evidence of metastatic disease with computed tomography scan of the chest and radionuclide bone scan, or Positron Emission Tomography (PET/CT) within 2 weeks of entry; No prior therapy; Eastern Cooperative Oncology Group performance status 0-1; Life expectancy >3 months; Adequate renal, hepatic, and hemopoietic function; Exclusion Criteria: Previously treated by chemotherapy or unplanned surgery in other hospital; Have had other kinds of malignant tumors at the same time; Uncontrolled complications, such as diabetes mellitus and so on; Intravascular tumor thrombus on enhanced CT or magnetic resonance (MR); Unresectable disease evaluated by surgeons.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre surgical Chemotherapy<br>Immediate pre surgical chemotherapy treated with four drugs including doxorubicin, cisplatin, high-dose methotrexate (MTX) and ifosfamide in eleven weeks, and then definitive surgery followed by adjuvant chemotherapy according to chemotherapy regimen in Peking University People's Hospital(PKUPH). | Drug: Doxorubicin<br>* 60mg/m^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: Adriamycin;Drug: Cisplatin<br>* 100mg/m^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: platamin;Drug: Methotrexate<br>* High dose of methotrexate (8-12g/m^2), in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: HD-MTX;Drug: Ifosfamide<br>* 12g/m^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: ifosphamide;Procedure: definitive surgery<br>* Including limb-sparing procedure and amputation<br>Other: pre surgical chemotherapy<br>* chemotherapy that given before definitive surgery<br>* Other names: neoadjuvant chemotherapy;|
| Other: Immediate Surgery<br>Immediate definitive surgery, and then post operative chemotherapy based on doxorubicin, cisplatin, high-dose MTX and ifosfamide according to chemotherapy regimen in PKUPH. | Drug: Doxorubicin<br>* 60mg/m^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: Adriamycin;Drug: Cisplatin<br>* 100mg/m^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: platamin;Drug: Methotrexate<br>* High dose of methotrexate (8-12g/m^2), in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: HD-MTX;Drug: Ifosfamide<br>* 12g/m^2, in the adjuvant chemotherapy regimen for osteosarcoma in PKUPH<br>* Other names: ifosphamide;Procedure: definitive surgery<br>* Including limb-sparing procedure and amputation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Calculated from the date of treatment start until death, whichever comes first. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Calculated from the date of treatment start until the time of disease progression or death, whichever comes first. | 5 years | 
| Tumor necrosis rate | The percentage of tumor necrosis calculated in the resected specimen in Arm 2. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteosarcoma, pelvis, sacrum