Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
Condition: Adult Alveolar Soft-part Sarcoma; Adult Angiosarcoma; Adult Epithelioid Sarcoma; Adult Extraskeletal Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Fibrous Histiocytoma; Adult Malignant Hemangiopericytoma; Adult Malignant Mesenchymoma; Adult Neurofibrosarcoma; Adult Synovial Sarcoma; Childhood Alveolar Soft-part Sarcoma; Childhood Angiosarcoma; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Neurofibrosarcoma; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Metastatic Childhood Soft Tissue Sarcoma; Nonmetastatic Childhood Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma
MeSH terms: Sarcoma; Osteosarcoma; Leiomyosarcoma; Liposarcoma; Chondrosarcoma; Sarcoma, Synovial; Hemangiosarcoma; Fibrosarcoma; Sarcoma, Alveolar Soft Part; Histiocytoma; Hemangiopericytoma; Solitary Fibrous Tumors; Histiocytoma, Benign Fibrous; Histiocytoma, Malignant Fibrous; Neurofibrosarcoma; Mesenchymoma; Dermatofibrosarcoma
Intervention: doxorubicin hydrochloride; clinical observation; therapeutic conventional surgery; 3-dimensional conformal radiation therapy; ifosfamide
Intervention description: Given IV; Patients undergo observation; Patients undergo surgery; Patients undergo radiotherapy; Given IV
Intervention MeSH terms: Doxorubicin; Liposomal doxorubicin; Ifosfamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 588.0
Sex: All
Maximum age: 29 Years
Healthy volunteers: No

Summary:

      This phase III trial is studying observation to see how well a risk based treatment strategy
      works in patients with soft tissue sarcoma. In the study, patients are assigned to receive
      surgery +/- radiotherapy +/- chemotherapy depending on their risk of recurrence. Sometimes,
      after surgery, the tumor may not need additional treatment until it progresses. In this case,
      observation may be sufficient. Radiation therapy uses high-energy x-rays to kill tumor cells.
      Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to
      stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller
      and reduce the amount of normal tissue that needs to be removed. Giving these treatments
      after surgery may kill any tumor cells that remain after surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Newly diagnosed non-rhabdomyosarcoma soft tissue sarcoma (STS), confirmed by central
             pathology review via concurrent enrollment on protocol COG-D9902

               -  Metastatic or non metastatic disease

          -  Meets 1 of the following criteria:

               -  Intermediate (i.e., rarely metastasizing) or malignant STS, including any of the
                  following:

                    -  Adipocytic tumor, including liposarcoma of any of the following histology
                       subtypes:

                         -  Dedifferentiated

                         -  Myxoid

                         -  Round cell

                         -  Pleomorphic type

                         -  Mixed-type

                         -  Not otherwise specified (NOS)

                    -  Fibroblastic/myofibroblastic tumors, including any of the following:

                         -  Solitary fibrous tumor

                         -  Hemangiopericytoma

                         -  Low-grade myofibroblastic sarcoma

                         -  Myxoinflammatory fibroblastic sarcoma

                         -  Adult fibrosarcoma*

                         -  Myxofibrosarcoma

                         -  Low-grade fibromyxoid sarcoma or hyalinizing spindle-cell tumor

                         -  Sclerosing epithelioid fibrosarcoma

                    -  So-called fibrohistiocytic tumors, including any of the following:

                         -  Plexiform fibrohistiocytic tumor

                         -  Giant cell tumor of soft tissues

                         -  Pleomorphic malignant fibrous histiocytoma (MFH)/undifferentiated
                            pleomorphic sarcoma

                         -  Giant cell MFH/undifferentiated pleomorphic sarcoma with giant cells

                         -  Inflammatory MFH/undifferentiated pleomorphic sarcoma with prominent
                            inflammation

                    -  Smooth muscle tumor (leiomyosarcoma)

                    -  Pericytic [perivascular] tumor (malignant glomus tumor or glomangiosarcoma)

                    -  Vascular tumor, including angiosarcoma

                    -  Chondro-osseous tumors of any of the following types:

                         -  Mesenchymal chondrosarcoma

                         -  Extraskeletal osteosarcoma

                    -  Tumors of uncertain differentiation, including any of the following:

                         -  Angiomatoid fibrous histiocytoma

                         -  Ossifying fibromyxoid tumor

                         -  Myoepithelioma/parachordoma

                         -  Synovial sarcoma

                         -  Epithelioid sarcoma

                         -  Alveolar soft-part sarcoma

                         -  Clear cell sarcoma of soft tissue

                         -  Extraskeletal myxoid chondrosarcoma ("chordoid type")

                         -  Malignant mesenchymoma

                         -  Neoplasms with perivascular epithelioid cell differentiation (PEComa)

                         -  Clear cell myomelanocytic tumor

                         -  Intimal sarcoma

               -  Malignant peripheral nerve sheath tumor

               -  Dermatofibrosarcoma protuberans meeting both of the following criteria:

                    -  Non metastatic disease

                    -  Tumor must be grossly resected prior to study enrollment

               -  Embryonal sarcoma of the liver

               -  Unclassified STS that is too undifferentiated to be placed in a specific
                  pathologic category (undifferentiated STS or STS NOS)

          -  Gross resection of the primary tumor ≤ 42 days prior to enrollment required except if
             any of the following circumstances apply:

               -  Non metastatic high-grade tumor > 5 cm in maximal diameter and gross or
                  microscopic residual tumor is anticipated after resection

               -  Tumor of either high- or- low-grade that cannot be grossly excised without
                  unacceptable morbidity

               -  High-grade tumor with metastases

                    -  Patients with metastatic low-grade tumor whose disease is amenable to gross
                       resection at all sites must undergo gross resection of all sites prior to
                       study entry

          -  Patients with a tumor recurrence after a gross total resection are not eligible

          -  Tumors arising in bone are not eligible

          -  Patients with epithelioid sarcoma, clear cell sarcoma, or clinical or radiologic
             evidence of regional lymph node enlargement must undergo sentinel lymph node biopsies
             or lymph node sampling to confirm the status of regional lymph nodes* NOTE: *Except in
             cases where the study radiologist reviews the imaging and indicates that a biopsy is
             not needed to confirm that the patient has lymph node involvement.

               -  If lymph node biopsies are positive for tumor (or the lymph nodes are classified
                  as positive by the study radiologist), formal lymph node dissection must be done
                  at the time of definitive surgery(prior to study entry for patients assigned to
                  study regimen C)

          -  Patients with metastatic disease must undergo a biopsy to confirm the presence of
             metastatic tumor if all metastases are < 1 cm in maximal diameter (except in cases
             where the study radiologist reviews the imaging and indicated that a biopsy is not
             needed to confirm that the patient has metastatic disease)

          -  Lansky performance status (PS) 50-100% (for patients ≤ 16 years of age) OR Karnofsky
             PS 50-100% (for patients > 16 years of age)

          -  Life expectancy ≥ 3 months

          -  Absolute neutrophil count ≥ 1,000/mm³*

          -  Platelet count ≥ 100,000/mm³*

          -  Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (≥ 40
             mL/min for infants < 1 year of age)* or serum creatinine based on age and/or gender as
             follows:

               -  0.4 mg/dL (1 month to < 6 months of age)

               -  0.5 mg/dL (6 months to < 1 year of age)

               -  0.6 mg/dL (1 year to < 2 years of age)

               -  0.8 mg/dL (2 years to < 6 years of age)

               -  1.0 mg/dL (6 years to < 10 years of age)

               -  1.2 mg/dL (10 years to < 13 years of age)

               -  1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)

               -  1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

          -  Patients with urinary tract obstruction by tumor must meet the renal function criteria
             listed above AND must have unimpeded urinary flow established via decompression of the
             obstructed portion of the urinary tract

          -  Bilirubin ≤ 1.5 times upper limit of normal (ULN)*

          -  Shortening fraction ≥ 27% by echocardiogram* OR ejection fraction ≥ 50% by
             radionuclide angiogram*

          -  Not pregnant or nursing (patients undergoing radiotherapy and/or chemotherapy)

               -  No nursing for ≥ 1 month after completion of study treatment in study regimens C
                  or D

          -  Fertile patients must use effective contraception during and for ≥ 1 month after
             completion of study treatment

          -  Negative pregnancy test

          -  No evidence of dyspnea at rest*

          -  No exercise intolerance*

          -  Resting pulse oximetry reading > 94% on room air (for patients with respiratory
             symptoms)*

          -  Prior treatment for cancer allowed provided the patient meet the prior therapy
             requirements

          -  No prior anthracycline (e.g., doxorubicin or daunorubicin) or ifosfamide chemotherapy
             for patients enrolled on arm C or arm D

          -  No prior radiotherapy to tumor-involved sites