Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002898
Status:
COMPLETED
Last Update Posted:
2013-12-04
First Post:
1999-11-01
Brief Title:
Surgery Followed by Chemotherapy in Treating Young Patients With Soft Tissue Sarcoma
Sponsor:
Societe Internationale dOncologie Pediatrique
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
MMT 95 Study For Rhabdomyosarcoma and Other Malignant Soft Tissue Tumors of Childhood
Status:
COMPLETED
Status Verified Date:
1999-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 andor 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 andor additional surgery to compare how well they work in treating patients with soft tissue sarcoma
PURPOSE This randomized phase III trial is studying surgery followed by different regimens of combination chemotherapy given together with radiation therapy andor 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 CEVIVE 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 eg 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 III 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 investigators 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
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 CEVIVE 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 eg 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 III 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 investigators 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
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| EU-96035 | None | None | None |
| SIOP-MMT-95 | None | None | None |