NCT00379457 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Young Patients With Nonmetastatic Rhabdomyosarcoma

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: UNKNOWN
Registry last update: 2013-08-12

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating rhabdomyosarcoma. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to compare how well they work in treating young patients with nonmetastatic rhabdomyosarcoma.

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 rhabdomyosarcoma (RMS) or other malignant mesenchymal tumor, including undifferentiated soft tissue sarcoma or ectomesenchymoma * Has undergone diagnostic surgery within the past 8 weeks * Meets criteria for 1 of the following risk groups: * Low-risk group * Localized nonalveolar RMS at any site * Embryonal, spindle cell, or botryoid RMS (favorable pathology) * Microscopically completely resected disease (Intergroup Rhabdomyosarcoma Study \[IRS\] group I) * Negative nodes (N0) * Tumor size ≤ 5 cm AND age \< 10 years (favorable tumor size and age) * Standard-risk group, meeting criteria for 1 of the following subgroups: * Subgroup B * Localized nonalveolar RMS at any site * Favorable pathology * Microscopically completely resected disease (IRS group I) * N0 disease * Tumor size \> 5 cm OR age ≥ 10 years (unfavorable tumor size or age) * Subgroup C * Localized nonalveolar RMS in orbit, head and neck nonparameningeal sites, or genitourinary (GU) non bladder prostate (i.e., paratesticular and vagina/uterus) sites (favorable site) * Favorable pathology * Microscopic residual disease (pT3a) or completely resected disease with nodal involvement (N1) (IRS group II) OR macroscopic residual disease (pT3b) (IRS group III) * N0 disease * Any tumor size or age * Subgroup D * Localized nonalveolar RMS in parameningeal sites, extremities, GU bladder prostate sites, or other sites (unfavorable site) * Favorable pathology * IRS group II or III * N0 disease * Favorable tumor size and age * High-risk group, meeting criteria for 1 of the following subgroups: * Subgroup E * Localized nonalveolar RMS at unfavorable site * Favorable pathology * IRS group II or III * N0 disease * Unfavorable tumor size or age * Subgroup F * Localized nonalveolar RMS at any site * Favorable pathology * IRS group I, II, or III * Positive nodes (N1) * Any tumor size or age * Subgroup G * Localized alveolar RMS at any site * Alveolar RMS, including the solid-alveolar variant (unfavorable pathology) * IRS group I, II, or III * N0 disease * Any tumor size or age * Very high-risk group * Localized alveolar RMS at any site * Unfavorable pathology * IRS group I, II, or III * N1 disease * Any tumor size or age * Previously untreated disease (except for primary surgery) * No evidence of metastatic disease PATIENT CHARACTERISTICS: * Shortening fraction \> 28% * Ejection fraction \> 47% * No prior cardiac disease * Renal function must be equivalent to grade 0-1 nephrotoxicity * No prior malignant tumors * No pre-existing illness preventing treatment PRIOR CONCURRENT THERAPY: * See Disease Characteristics
healthy Volunteers: false
maximum Age: 20 Years
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

interventions

name
dactinomycin
type
BIOLOGICAL
name
carboplatin
type
DRUG
name
cyclophosphamide
type
DRUG
name
doxorubicin hydrochloride
type
DRUG
name
etoposide
type
DRUG
name
ifosfamide
type
DRUG
name
topotecan hydrochloride
type
DRUG
name
vincristine sulfate
type
DRUG
name
vinorelbine tartrate
type
DRUG
name
conventional surgery
type
PROCEDURE
name
radiation therapy
type
RADIATION

Study design

allocation: RANDOMIZED
primary Purpose: TREATMENT

Enrollment

count: 600
type: ESTIMATED

Registered outcome plans (not posted results)

primary Outcomes

measure
Event-free survival
measure
Disease-free survival (in patients treated with maintenance chemotherapy)

secondary Outcomes

measure
Overall survival
measure
Progression-free survival
measure
Response rate
measure
Toxicity as measured by NCI-CTC version 3

Full study description

brief Summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating rhabdomyosarcoma. PURPOSE: This randomized phase III trial is studying different combination chemotherapy regimens to compare how well they work in treating young patients with nonmetastatic rhabdomyosarcoma.
detailed Description: OBJECTIVES: * Improve the outcome in pediatric patients with low-risk rhabdomyosarcoma (RMS) treated with vincristine and dactinomycin alone. * Evaluate whether the outcome for older patients with standard-risk RMS with favorable features may be improved/maintained by administering a treatment with limited intensity. * Evaluate whether chemotherapy intensity for patients with standard-risk RMS can be reduced, by lowering the cumulative dose of ifosfamide. * Evaluate whether treatment can be reduced in a subgroup of patients with standard-risk RMS arising in an unfavorable site (e.g., parameningeal or other site) but with favorable site and age. * Compare the value of standard chemotherapy comprising ifosfamide, vincristine, and dactinomycin with vs without doxorubicin (as early intensification in the initial part of treatment) in patients with high-risk RMS. * Determine the role of low-dose maintenance chemotherapy comprising 6 months of cyclophosphamide and vinorelbine in patients with high-risk RMS. * Improve the results in patients with poor prognosis (very high-risk) RMS treated with more intensive ifosfamide, vincristine, dactinomycin, and doxorubicin followed by maintenance chemotherapy. OUTLINE: This is a non-blinded, randomized, prospective, multicenter study. Patients are stratified according to risk group (low risk vs standard risk vs high risk vs very high risk) and participating country. * Stratum 1 (low-risk group): Patients receive vincristine IV on day 1 in weeks 1-4, 7-10, 13-16, and 19-22 and dactinomycin IV on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22. * Stratum 2 (standard-risk group): Patients are assigned to 1 of 3 treatment groups according to their standard-risk subgroup. * Subgroup B: Patients receive ifosfamide IV over 3 hours on days 1 and 2 in weeks 1, 4, 7, and 10; vincristine IV on day 1 in weeks 1-7, 10, 13, 16, 19, 22, and 25; and dactinomycin IV on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, 22, and 25. * Subgroup C: Patients receive ifosfamide IV over 3 hours on days 1 and 2 in weeks 1, 4, and 7; vincristine IV on day 1 in weeks 1-7; and dactinomycin IV on day 1 in weeks 1, 4, and 7. Patients are evaluated for tumor response in week 9. Patients in complete remission (CR) with favorable age and tumor size continue to receive ifosfamide, vincristine, and dactinomycin as above in weeks 10, 13, 16\*, 19, 22, and 25. Patients may also undergo radiotherapy beginning in week 13 and continuing for 5-6 weeks. Patients in CR with unfavorable age or tumor size OR in partial remission (PR) (i.e., \> 1/3 tumor volume reduction) continue to receive ifosfamide as above in weeks 10 and 16 and vincristine and dactinomycin as above in weeks 10, 13, 16\*, 19, 22, and 25. These patients also undergo radiotherapy beginning in week 13 and continuing for 5-6 weeks. Patients with stable or progressive disease in week 9 proceed to second-line therapy and radiotherapy. Patients with residual disease after completion of chemotherapy in week 10 undergo surgical resection followed by ifosfamide, vincristine, and dactinomycin (with or without radiotherapy) as above in weeks 13, 16\*, 19, 22, and 25. * Subgroup D: Patients receive ifosfamide IV over 3 hours on days 1 and 2 in weeks 1, 4, and 7; vincristine IV on day 1 in weeks 1-7; and dactinomycin IV on day 1 in weeks 1, 4, and 7. Patients are evaluated for tumor response in week 9. Patients in CR or PR continue to receive ifosfamide, vincristine, and dactinomycin as above in weeks 10, 13, 16\*, 19, 22, and 25. Patients may also undergo radiotherapy beginning in week 13 and continuing for 5-6 weeks. Patients with stable or progressive disease in week 9 proceed to second-line therapy and radiotherapy. Patients with residual disease after completion of chemotherapy in week 10 undergo surgical resection followed by ifosfamide, vincristine, and dactinomycin (with or without radiotherapy) as above in weeks 13, 16\*, 19, 22, and 25. NOTE: \*Dactinomycin may be omitted during radiotherapy in week 16. * Stratum 3 (high-risk group): Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive ifosfamide, vincristine, and dactinomycin as in subgroups C and D of stratum 2. Patients are evaluated for tumor response in week 9. Patients in CR or PR continue to receive ifosfamide, vincristine, and dactinomycin as in subgroups C and D of stratum 2. Patients may also undergo radiotherapy beginning in week 13 and continuing for 5-6 weeks. Patients with stable or progressive disease in week 9 proceed to second-line therapy and radiotherapy. Patients with residual disease after completion of chemotherapy in week 10 undergo surgical resection followed by ifosfamide, vincristine, and dactinomycin (with or without radiotherapy) as above in weeks 13, 16\*, 19, 22, and 25. * Arm II: Patients receive ifosfamide, vincristine, and dactinomycin as in subgroups C and D of stratum 2. Patients also receive doxorubicin IV over 4 hours on days 1 and 2 in weeks 1, 4, and 7. Patients are evaluated for tumor response in week 9. Patients in CR or PR continue to receive ifosfamide, vincristine, dactinomycin, and doxorubicin as above in week 10 and then ifosfamide, vincristine, and dactinomycin as above in weeks 13, 16\*, 19, 22, and 25. Patients may also undergo radiotherapy beginning in week 13 and continuing for 5-6 weeks. Patients with stable or progressive disease in week 9 proceed to second-line therapy and radiotherapy. Patients with residual disease after completion of chemotherapy in week 10 undergo surgical resection followed by ifosfamide, vincristine, and dactinomycin (with or without radiotherapy) as above in weeks 13, 16\*, 19, 22, and 25. NOTE: \*Dactinomycin may be omitted during radiotherapy in week 16. * Maintenance chemotherapy: Patients who remain in CR or with minimal abnormalities on imaging studies after completion of therapy according to their randomized arm (as above) undergo a second randomization. Randomization occurs within 6 weeks after administration of the last course of chemotherapy on arm I or II. * Arm I: Patients receive no maintenance chemotherapy. * Arm II: Patients receive vinorelbine IV over 5-10 minutes on days 1, 8, and 15 and oral cyclophosphamide once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses. * Stratum 4 (very high-risk group): Patients receive ifosfamide, vincristine, and dactinomycin as in subgroups C and D of stratum 2. Patients also receive doxorubicin as in arm II of stratum 3. Patients are evaluated for tumor response in week 9. Patients in CR or PR continue to receive ifosfamide, vincristine, dactinomycin, and doxorubicin as in arm II of stratum 3. Patients may also undergo radiotherapy beginning in week 13 and continuing for 5-6 weeks. Patients with stable or progressive disease in week 9 proceed to second-line therapy and radiotherapy. Patients with residual disease after completion of chemotherapy in week 10 undergo surgical resection followed by ifosfamide, vincristine, and dactinomycin (with or without radiotherapy) as above in weeks 13, 16, 19, 22, and 25. After completion of chemotherapy, patients with a limited quantity of viable tumor proceed to maintenance chemotherapy. * Maintenance chemotherapy: Patients receive vinorelbine IV over 5-10 minutes on days 1, 8, and 15 and oral cyclophosphamide once daily on days 1-28. Treatment repeats every 28 days for up to 6 courses. * Second-line therapy: Patients in any stratum with stable or progressive disease in week 9 receive 1 of 2 second-line therapy regimens. * Regimen 1: Patients receive topotecan IV on days 1-3 and carboplatin IV on days 4 and 5 in weeks 1 and 4. Patients are then evaluated for tumor response. Patients with good response receive topotecan IV on days 1-3 and cyclophosphamide IV on days 1 and 2 in weeks 7 and 13 and etoposide IV on days 1-3 and carboplatin IV on days 4 and 5 in weeks 10 and 16. Patients with no response receive local therapy or a new chemotherapy regimen. * Regimen 2: Patients receive doxorubicin IV on day 1 and carboplatin IV on days 1 and 2 in weeks 1 and 4. Patients are then evaluated for tumor response. Patients with good response receive doxorubicin IV on day 1 in weeks 7, 10, 13, and 16; cyclophosphamide IV on days 1 and 2 in weeks 7 and 13; and carboplatin IV on days 1 and 2 of weeks 10 and 16. Patients with no response receive local therapy or a new chemotherapy regimen. After completion of therapy, patients are followed periodically for at least 5 years. PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study.

Source references

references

citation
Orbach D, Van Noesel MM, Brennan B, Corradini N, Alaggio R, Ben Arush M, Schoot RA, Berlanga P, Zanetti I, Hjalgrim LL, Di Corti F, Ramirez G, Casanova M, Ferrari A. Epithelioid hemangioendothelioma in children: The European Pediatric Soft Tissue Sarcoma Study Group experience. Pediatr Blood Cancer. 2022 Oct;69(10):e29882. doi: 10.1002/pbc.29882. Epub 2022 Jul 16.
pmid
35841307
type
DERIVED
citation
Schoot RA, Chisholm JC, Casanova M, Minard-Colin V, Geoerger B, Cameron AL, Coppadoro B, Zanetti I, Orbach D, Kelsey A, Rogers T, Guizani C, Elze M, Ben-Arush M, McHugh K, van Rijn RR, Ferman S, Gallego S, Ferrari A, Jenney M, Bisogno G, Merks JHM. Metastatic Rhabdomyosarcoma: Results of the European Paediatric Soft Tissue Sarcoma Study Group MTS 2008 Study and Pooled Analysis With the Concurrent BERNIE Study. J Clin Oncol. 2022 Nov 10;40(32):3730-3740. doi: 10.1200/JCO.21.02981. Epub 2022 Jun 16.
pmid
35709412
type
DERIVED

Source notices and limitations

Discovery and provenance

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analysis of 109 patients with rhabdomyosarcoma with extremity primary tumors distal to the elbow or knee who were treated in the EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> trial (2005–2016).[<a href="#cit/section_1.91">91</a>] Thirty-seven of 109 patients (34%) had lymph node metastases at diagno
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s with rhabdomyosarcoma with extremity primary tumors distal to the elbow or knee who were treated in the EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> trial (2005–2016).[<a href="#cit/section_1.91">91</a>] Thirty-seven of 109 patients (34%) had lymph node metastases at diagnosis. Of the 37 patients
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resence of metastatic disease. These investigators also studied the diagnostic potential of ctDNA in 57 patients enrolled in the EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study. ctDNA was detected using both shallow whole-genome sequencing (WGS) and cell-free reduced representation bisulfite sequenci
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isease. These investigators also studied the diagnostic potential of ctDNA in 57 patients enrolled in the EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study. ctDNA was detected using both shallow whole-genome sequencing (WGS) and cell-free reduced representation bisulfite sequencing (cfRRBS). Of the 25
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of the chest.The European Paediatric Soft Tissue Sarcoma Study Group reviewed 367 patients enrolled in the <a href="/clinicaltrials/NCT00379457">CCLG-EPSSG-RMS-2005 (NCT00379457)</a> study.[<a href="#cit/section_3.1">1</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810033&version=HealthProfess
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="-1">The European Paediatric Soft Tissue Sarcoma Study Group reviewed 367 patients enrolled in the <a href="/clinicaltrials/NCT00379457">CCLG-EPSSG-RMS-2005 (NCT00379457)</a> study.[<a href="#cit/section_3.1">1</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810033&version=HealthProfessional&language=English" onclick
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the use of early local therapy, including RT.[<a href="#cit/section_4.1">1</a>-<a href="#cit/section_4.3">3</a>]</li><li>The EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study reported comprehensive outcome data for 1,733 children and adolescents with nonmetastatic rhabdomyosarcoma. These patients we
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therapy, including RT.[<a href="#cit/section_4.1">1</a>-<a href="#cit/section_4.3">3</a>]</li><li>The EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study reported comprehensive outcome data for 1,733 children and adolescents with nonmetastatic rhabdomyosarcoma. These patients were enrolled in two phas
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th superficial tumors is consistent with good cosmetic and functional results. The EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study prospectively enrolled 165 patients with localized head and neck, nonparameningeal rhabdomyosarcoma. Local therapy included s
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s consistent with good cosmetic and functional results. The EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study prospectively enrolled 165 patients with localized head and neck, nonparameningeal rhabdomyosarcoma. Local therapy included surgery (58%) and/or RT
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erineal 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%. Eighty-seven percent of patients with relapse or disease progression
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longer recommended for scrotal violation.[<a href="#cit/section_6.122">122</a>] The EpSSG <a href="/clinicaltrials/NCT00379457">RMS-2005 (NCT00379457)</a> study enrolled 237 patients with paratesticular tumors. Seventy-five patients (32%) had an inappropriate first surgery, defined as
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Updated: April 11, 2025
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April 11, 2025
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Preserved source evidence · Not medical advice