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NCT00002898 · CITED IN SOURCE DOCUMENTS

Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2013-12-04

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug with surgery and/or radiation therapy may kill more tumor cells. PURPOSE: This randomized phase III trial is studying surgery followed by different regimens of combination chemotherapy given together with radiation therapy and/or additional surgery to compare how well they work in treating patients with soft tissue sarcoma.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed primary soft tissue sarcoma: * Rhabdomyosarcoma * Non-rhabdomyosarcoma * Soft tissue primitive neuroectodermal tumor (PNET) * Extraosseous Ewing's sarcoma PATIENT CHARACTERISTICS: Age: * Under 18 Performance status: * Not specified Life expectancy: * Not specified Hematopoietic: * Not specified Hepatic: * Not specified Renal: * Not specified PRIOR CONCURRENT THERAPY: Biologic: * Not specified Chemotherapy: * Not specified Endocrine: * Not specified Radiotherapy: * Not specified Surgery: * Prior primary surgery allowed Other: * No other prior therapy
healthy Volunteers
false
maximum Age
17 Years
sex
ALL
std Ages
  1. CHILD
Treatment arms and interventions
interventions
  1. name
    dactinomycin
    type
    BIOLOGICAL
  2. name
    carboplatin
    type
    DRUG
  3. name
    cyclophosphamide
    type
    DRUG
  4. name
    epirubicin hydrochloride
    type
    DRUG
  5. name
    etoposide
    type
    DRUG
  6. name
    ifosfamide
    type
    DRUG
  7. name
    vincristine sulfate
    type
    DRUG
  8. name
    adjuvant therapy
    type
    PROCEDURE
  9. name
    conventional surgery
    type
    PROCEDURE
  10. name
    neoadjuvant therapy
    type
    PROCEDURE
  11. name
    brachytherapy
    type
    RADIATION
  12. name
    radiation therapy
    type
    RADIATION
Study design
allocation
RANDOMIZED
primary Purpose
TREATMENT
Enrollment
count
400
type
ESTIMATED
Registered outcome plans (not posted results)
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug with surgery and/or radiation therapy may kill more tumor cells. PURPOSE: This randomized phase III trial is studying surgery followed by different regimens of combination chemotherapy given together with radiation therapy and/or additional surgery to compare how well they work in treating patients with soft tissue sarcoma.
detailed Description
OBJECTIVES: * Assess whether good survival rates can be maintained for patients with stage I (pathologic T1) soft tissue sarcomas (STS) treated with limited chemotherapy after complete surgical resection, and whether disease-free survival can be improved by improving the precision of pretreatment staging and the assessment of the completeness of the resection. * Compare the survival of patients with high-risk nonmetastatic STS treated with alternating regimens of carboplatin, epirubicin, and vincristine (CEV) and ifosfamide, vincristine, and etoposide (IVE) vs continuation of ifosfamide, vincristine, and dactinomycin (IVA) after initial therapy with IVA. * Assess whether the improved outcome seen for patients with stage III (node positive) STS in an earlier protocol (SIOP-MMT-89) can be maintained with 3 courses of alternating CEV/IVE without altering local therapy. * Compare outcome of patients with nonmetastatic STS to those with stage IV STS who are registered on this protocol but referred to treatment on the European Intergroup Stage IV Study. * Assess survival and the risk of late sequelae in patients with non-rhabdomyosarcoma malignant mesenchymal tumors treated on this protocol. * Evaluate the role of neoadjuvant chemotherapy, new prognostic factors (e.g., ploidy, histologic grading), and recommendations for the management of fibrosarcoma in infants and of fibromatoses. * Assess ifosfamide nephrotoxicity based on total dose administered and the long-term toxicity based on the potential predictive value of early evidence of nephrotoxicity. OUTLINE: This is a randomized study for patients with high-risk, nonmetastatic sarcoma, except those with the following characteristics: age less than 6 months, stage I/II non-alveolar orbital tumor, stage III disease, or age less than 3 years with parameningeal disease. Patients are stratified according to disease type (rhabdomyosarcoma (RMS) vs non-RMS disease), parameningeal site of disease, and participating center. Patients with RMS are further randomized by alveolar histology. Randomization occurs after the first course of chemotherapy. All patients, regardless of disease stage, are registered to this study and outcome is followed, although patients with metastatic RMS or non-RMS malignant mesenchymal tumors are referred for treatment on the SIOP-MMT-98 study. Patients diagnosed more than 8 weeks prior to entry or who are unavailable for follow-up are not treated on study. Doses are modified for patients under 1 year of age or under 10 kg of body weight. All other patients are assigned therapy based on risk group. After surgery, patients with complete resection and with proven or possible chemosensitive histologies proceed to chemotherapy on the low-risk regimen. Patients with questionable completeness of resection proceed to chemotherapy for standard-risk or high-risk tumors, as appropriate. Regardless of resection results, patients who underwent scrotal surgery for paratesticular tumors proceed to chemotherapy for standard-risk tumors. Alveolar RMS is considered high risk. LOW-RISK TUMORS (T1 N0 M0): Strategy 951 * Tumors must be resectable without extensive, mutilating surgery, and resection margins must be microscopically negative at all sites. Patients with positive margins may undergo re-excision. * Vincristine is administered weekly for 4 weeks with dactinomycin given on the same day as the first and fourth doses of vincristine. The course is repeated once after a 3-week rest. STANDARD-RISK TUMORS (T1-2 N0 M0): Strategy 952 * After resection as above, patients with incompletely resected T1 tumors, completely resected T1 tumors that extended beyond the tissue or organ of origin, or completely or incompletely resected T2 tumors at favorable sites (vagina, uterus, or paratesticular region) receive chemotherapy on this regimen. * Ifosfamide, vincristine, and dactinomycin (IVA) is started within 8 weeks of surgery and administered every 3 weeks for 3 courses; during this course only, vincristine is administered weekly throughout the 6 weeks. Response is assessed at week 8. * Patients with at least a 50% response at week 8 receive 3 more courses of IVA and are reassessed at week 17; those with a complete response (CR) discontinue treatment, while those with less than a CR begin local therapy (described below) on week 18 concurrently with 3 more courses of IVA (unless no further response was seen after week 8). * Patients with less than a 50% response at week 8 receive carboplatin, epirubicin, and vincristine (CEV) on weeks 9, 15, and 21 and ifosfamide, vincristine, and etoposide (IVE) on weeks 12, 18, and 24. Patients with less than a CR at week 17 receive concurrent local therapy beginning at week 18. HIGH-RISK TUMORS: Strategy 953 * Patients with high-risk tumors after surgery are randomized to IVA as in strategy 952 (Arm I) or to 3 weeks of IVA (1 course) as in Strategy 952 followed by CEV and IVE as in Strategy 952 (Arm II). Response is assessed at week 8. Patients with parameningeal disease who are at least 3 years of age proceed to radiotherapy at week 9, regardless of response. * Patients on Arm I with at least a 50% response at week 8 receive 3 more courses of IVA and are reassessed at week 17; those who continue to respond between weeks 8 and 17 receive 3 additional courses of IVA. Patients with no further response receive 4 alternating courses of CEV and IVE. All patients with less than a CR at week 17 begin local therapy on week 18 concurrently with the additional chemotherapy. Patients on Arm I with less than a 50% response at week 8 receive alternating CEV and IVE as in Strategy 952. Patients with less than a CR at week 17 begin concurrent local therapy at week 18. * Patients on Arm II who have at least a 50% response at week 8 continue treatment with 2 courses of sequential IVA, CEV, and IVE. Local therapy is concurrently administered, beginning on week 18, to patients who have not achieved a CR by week 17. Patients on Arm II who have less than a 50% response at week 8 proceed immediately to local therapy with additional chemotherapy at the investigator's discretion. Patients with less than a CR after local therapy are considered for treatment on a phase II protocol. LOCAL THERAPY * Local therapy consists of conservative resection of residual disease (unless more debilitating surgery is appropriate). Patients with residual disease after surgery undergo external-beam radiotherapy 5 days per week for 6-7 weeks or brachytherapy; hyperfractionation is specifically excluded. For patients receiving radiotherapy, the dactinomycin dose in the IVA regimen is omitted from the middle course of chemotherapy and possibly the last course of chemotherapy during concurrent administration. Patients receiving alternating CEV and IVE have the courses reversed during concurrent radiotherapy, with possible omission of epirubicin for the third course. * Radical surgery is considered for any patient who has residual disease at week 27. TREATMENT FOR RELAPSE * Patients treated with Strategy 951 proceed to therapy with at least 6 alternating courses of IVE and CEV, with local therapy initiated after the second course. Other patients receive at least 6 alternating courses of CEV and vincristine, carboplatin, and etoposide (modified Vincaepi), with local therapy initiated after the second course. Patients who have already received either regimen may be re-treated with carboplatin and etoposide and vincristine and cyclophosphamide if relapse occurs more than 6 months after treatment, while those who relapse in less than 6 months are considered for phase II chemotherapy trials. Patients with metastatic relapse are evaluated for bone marrow or peripheral blood stem cell transplantation. Patients are followed every 2 months until 2 years after diagnosis, every 3 months for 1 year, every 6 months for 2 years, and then annually until 10 years after diagnosis. PROJECTED ACCRUAL: A total of 400 patients with high-risk nonmetastatic disease will be accrued for this study within approximately 4 years.
Source references
references
  1. citation
    Chisholm JC, Marandet J, Rey A, Scopinaro M, de Toledo JS, Merks JH, O'Meara A, Stevens MC, Oberlin O. Prognostic factors after relapse in nonmetastatic rhabdomyosarcoma: a nomogram to better define patients who can be salvaged with further therapy. J Clin Oncol. 2011 Apr 1;29(10):1319-25. doi: 10.1200/JCO.2010.32.1984. Epub 2011 Feb 28.
    pmid
    21357778
    type
    BACKGROUND
  2. citation
    Orbach D, Mc Dowell H, Rey A, Bouvet N, Kelsey A, Stevens MC. Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group. Pediatr Blood Cancer. 2011 Dec 15;57(7):1130-6. doi: 10.1002/pbc.23138. Epub 2011 Apr 14.
    pmid
    21495161
    type
    BACKGROUND
  3. citation
    Defachelles AS, Rey A, Oberlin O, Spooner D, Stevens MC. Treatment of nonmetastatic cranial parameningeal rhabdomyosarcoma in children younger than 3 years old: results from international society of pediatric oncology studies MMT 89 and 95. J Clin Oncol. 2009 Mar 10;27(8):1310-5. doi: 10.1200/JCO.2008.19.5701. Epub 2009 Feb 9.
    pmid
    19204197
    type
    BACKGROUND
  4. citation
    Oberlin O, Rey A, Sanchez de Toledo J, Martelli H, Jenney ME, Scopinaro M, Bergeron C, Merks JH, Bouvet N, Ellershaw C, Kelsey A, Spooner D, Stevens MC. Randomized comparison of intensified six-drug versus standard three-drug chemotherapy for high-risk nonmetastatic rhabdomyosarcoma and other chemotherapy-sensitive childhood soft tissue sarcomas: long-term results from the International Society of Pediatric Oncology MMT95 study. J Clin Oncol. 2012 Jul 10;30(20):2457-65. doi: 10.1200/JCO.2011.40.3287. Epub 2012 Jun 4.
    pmid
    22665534
    type
    RESULT
Source notices and limitations
    Discovery and provenance
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        nce C1</a>] </li><li>A retrospective review examined 50 patients with nonmetastatic perianal/perineal rhabdomyosarcoma treated in the <a href="/clinicaltrials/NCT00002898">SIOP-MMT-95 (NCT00002898)</a>, Italian RMS-96, and EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005</a> trials. The study found a 5-year EFS rate of 47.8%
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        trospective review examined 50 patients with nonmetastatic perianal/perineal rhabdomyosarcoma treated in the <a href="/clinicaltrials/NCT00002898">SIOP-MMT-95 (NCT00002898)</a>, Italian RMS-96, and EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005</a> trials. The study found a 5-year EFS rate of 47.8% and an OS rate of 52.6%.
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        ative efficacy of this approach versus the standard approach requires further investigation.</li></ul></div></li><li>A European trial (<a href="/clinicaltrials/NCT00002898">SIOP-MMT-95</a>) included 457 patients with incompletely resected embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, undifferentiated sarcoma, or soft tis
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      source update dates
      1. context
        Updated: April 11, 2025
        datetime
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        display
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    Preserved source evidence · Not medical advice