Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00346164
First received: June 28, 2006
Last updated: June 14, 2013
Last verified: June 2013
  Purpose

This phase III trial is studying observation to see how well it works compared with radiation therapy, combination chemotherapy, and/or surgery in treating patients with soft tissue sarcoma.

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. It is not yet known which regimen is more effective in treating soft tissue sarcoma.


Condition Intervention Phase
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
Chondrosarcoma
Dermatofibrosarcoma Protuberans
Localized Childhood Malignant Fibrous Histiocytoma of Bone
Metastatic Childhood Malignant Fibrous Histiocytoma of Bone
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
Drug: doxorubicin hydrochloride
Other: clinical observation
Procedure: therapeutic conventional surgery
Radiation: 3-dimensional conformal radiation therapy
Drug: ifosfamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Based Treatment for Non-Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS) in Patients Under 30 Years of Age

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Long-term survival for low-risk patients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A monitoring boundary located in some sense halfway between the O'Brien-Fleming and Pocock group sequential boundaries to monitor against the expected experience will be used. A procedure adapted from Woolson will be used.

  • Event-free and overall survival for patients in the intermediate risk group [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Because the planned therapy for these patients (ifosfamide/doxorubicin chemotherapy and radiotherapy) is presently considered a standard of care, no formal monitoring of event-free or overall survival of these patients is planned.


Secondary Outcome Measures:
  • Local failure rate [ Time Frame: Up to 5 years follow up ] [ Designated as safety issue: No ]
    The method of Woolson103 to assess evidence for an unacceptable isolated local failure rate will be used. Evaluation of the isolated local failure rate will take place after 15, 30, and 45 isolated local failures are observed using monitoring p-values of 0.023, 0.052, and 0.070.

  • Toxicity of neoadjuvant chemoradiotherapy [ Time Frame: Twice yearly beginning on week 16, assessed up to 5 years ] [ Designated as safety issue: Yes ]
    A monitoring boundary located halfway between the O'Brien-Fleming and Pocock group sequential boundaries and a spending function approach will be used for interim monitoring of toxicity.


Enrollment: 588
Study Start Date: February 2007
Estimated Primary Completion Date: January 2100 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1 (Observation or radiotherapy)

Patients with low-grade tumor with either negative or positive microscopic margins or high-grade tumor ≤ 5 cm (in maximum diameter) with negative microscopic margins are assigned to regimen A. Patients with high-grade tumor ≤ 5 cm (in maximum diameter) with positive microscopic margins are assigned to regimen B.

REGIMEN A (observation only): Patients undergo observation only.

REGIMEN B (adjuvant radiotherapy): Beginning between 6-42 days after surgical resection, patients undergo a total of 31 fractions of adjuvant radiotherapy.

Other: clinical observation
Patients undergo observation
Other Name: observation
Procedure: therapeutic conventional surgery
Patients undergo surgery
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Experimental: Group 2 (chemotherapy, radiotherapy, surgery)

REGIMEN C (adjuvant chemoradiotherapy): Patients receive ifosfamide IV; doxorubicin hydrochloride IV; beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy.

REGIMEN D (neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy with or without radiotherapy): Neoadjuvant chemoradiotherapy and surgery: Patients receive ifosfamide IV; doxorubicin hydrochloride IV. Beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy. Patients undergo surgical resection in week 13.

Adjuvant chemotherapy with or without radiotherapy: Patients receive ifosfamide IV and doxorubicin IV. Beginning in week 16, some patients undergo a total of 6 fractions of adjuvant radiotherapy and some patients undergo a total of 11 fractions of adjuvant radiotherapy. Patients achieving total gross resection with negative microscopic margins do not receive adjuvant radiotherapy

Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Procedure: therapeutic conventional surgery
Patients undergo surgery
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Experimental: Group 3 (observation, chemotherapy, radiotherapy, surgery)
(High risk [metastatic, resected, incompletely resected, or unresected disease]): Patients with low-grade, all-sites resected tumor with either negative or positive microscopic margins are assigned to receive treatment as in group 1 regimen A. Patients with high-grade, grossly resected primary tumor, with metastases are assigned to receive treatment as in group 2 regimen C. Patients with unresected, high-grade metastatic tumor are assigned to receive treatment as in group 2 regimen D.
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Other: clinical observation
Patients undergo observation
Other Name: observation
Procedure: therapeutic conventional surgery
Patients undergo surgery
Radiation: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy
Other Names:
  • 3D conformal radiation therapy
  • 3D-CRT
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 29 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)*
  • No concurrent aprepitant during chemotherapy
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00346164

  Show 187 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Sheri Spunt Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00346164     History of Changes
Other Study ID Numbers: ARST0332, NCI-2009-00426, COG-ARST0332, CDR0000483702, U10CA098543
Study First Received: June 28, 2006
Last Updated: June 14, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Histiocytoma
Histiocytoma, Benign Fibrous
Chondrosarcoma
Fibrosarcoma
Fibrosis
Hemangiopericytoma
Hemangiosarcoma
Leiomyosarcoma
Liposarcoma
Mesenchymoma
Osteosarcoma
Sarcoma, Synovial
Sarcoma
Dermatofibrosarcoma
Sarcoma, Alveolar Soft Part
Neurofibrosarcoma
Neurilemmoma
Histiocytoma, Malignant Fibrous
Liver Neoplasms
Neoplasms, Fibrous Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Pathologic Processes
Neoplasms, Vascular Tissue
Neoplasms, Muscle Tissue
Neoplasms, Adipose Tissue
Neoplasms, Complex and Mixed
Neoplasms, Bone Tissue

ClinicalTrials.gov processed this record on July 24, 2014