Ignite Creation Date:
2024-05-05 @ 11:20 AM
Last Modification Date:
2024-10-26 @ 9:03 AM
Study NCT ID:
NCT00002516
Status:
UNKNOWN
Last Update Posted:
2013-09-17
First Post:
1999-11-01
Brief Title:
Combination Chemotherapy Plus Surgery and Radiation Therapy in Treating Patients With Ewings Sarcoma
Sponsor:
University Hospital Muenster
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
EUROPEAN INTERGROUP COOPERATIVE EWINGS SARCOMA STUDY EICESS 92
Status:
UNKNOWN
Status Verified Date:
2010-01
Last Known Status:
ACTIVE_NOT_RECRUITING
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 Radiation therapy uses high-energy x-rays to damage tumor cells Combining more than one drug with surgery and radiation therapy may kill more tumor cells It is not yet known which combination chemotherapy regimen is most effective in treating patients with Ewings sarcoma
PURPOSE Randomized phase III trial to compare various combination chemotherapy regimens plus surgery and radiation therapy in treating patients who have Ewings sarcoma
PURPOSE Randomized phase III trial to compare various combination chemotherapy regimens plus surgery and radiation therapy in treating patients who have Ewings sarcoma
Detailed Description:
OBJECTIVES I Determine whether morbidity can be reduced while preserving survival by substituting cyclophosphamide for ifosfamide in adjuvant combination chemotherapy in standard-risk patients with Ewings sarcoma or peripheral neuroectodermal tumor PNET II Determine whether survival is improved without unacceptable toxicity for high-risk patients with Ewings sarcoma or PNET by the addition of etoposide to the VAIA regimen vincristinedoxorubicinifosfamidedactinomycin III Evaluate the impact of surgery and conventional vs hyperfractionated radiotherapy definitive and adjuvant on local control overall survival and morbidity in these patients IV Relate treatment outcome with patient characteristics histologic subtype at diagnosis and histologic response to neoadjuvant treatment V Evaluate prospectively ifosfamide-induced nephrotoxicity and doxorubicin-induced cardiotoxicity
OUTLINE Randomized study Patients are initially stratified as STANDARD RISK tumor volume at diagnosis 100 ml and HIGH RISK tumor volume at diagnosis at least 100 ml or if 100 ml metastasis present All patients receive 14 courses of chemotherapy administered q 3 weeks throughout protocol treatment Standard-risk patients receive 4 courses of NEOADJUVANT CHEMOTHERAPY on Regimen A while high-risk patients are randomized on Arms I and II for 4 courses of neoadjuvant chemotherapy LOCAL THERAPY is usually initiated on week 12 after 4 courses of neoadjuvant chemotherapy and consists of either total removal of the tumor-bearing compartment intracompartmental surgery with or without adjuvant radiotherapy or definitive radiotherapy alone the choice is dictated by the site tumor size and patient age among other variables Postoperatively all patients receive 10 courses of ADJUVANT CHEMOTHERAPY plus adjuvant radiotherapy when given standard-risk patients are randomized on Arms III and IV while high-risk patients receive the same regimen to which they were assigned at initial randomization When given adjuvant radiotherapy begins on week 19 and is administered concurrently with chemotherapy As a variant of this general plan patients with 50 regression of the soft tissue component of their tumors at restaging after 2 courses of neoadjuvant chemotherapy slow response may receive preoperative irradiation beginning on week 7 concomitantly with the third and fourth courses of chemotherapy The following acronyms are used CTX Cyclophosphamide NSC-26271 DACT Dactinomycin NSC-3053 DOX Doxorubicin NSC-123127 IFF Ifosfamide NSC-109724 Mesna Mercaptoethane sulfonate NSC-113891 VCR Vincristine NSC-67574 VP-16 Etoposide NSC-141540 NEOADJUVANT CHEMOTHERAPY Regimen A Standard risk Alternating 3-Drug Combination Chemotherapy Regimens VAIA VCRDOXIFF alternating with VCRDACTIFF Arm I High risk Alternating 3-Drug Combination Chemotherapy Regimens VAIA VCRDOXIFF alternating with VCRDACTIFF Arm II High-risk Alternating 4-Drug Combination Chemotherapy Regimens EVAIA VP-16VCRDOXIFF alternating with VP-16VCRDACTIFF LOCAL THERAPY Surgery Resection of entire tumor-bearing compartment including bone and soft tissue when possible is the treatment of choice The range of possible surgical procedures includes radical resection eg amputation wide resection en bloc removal of the entire tumor-bearing compartment marginal surgery en bloc removal but resection line runs through pseudocapsule and microscopic residual disease is likely intralesional resection tumor incised with contamination of surgical field and no resection Radiotherapy There are 3 settings in which radiotherapy is delivered in these patients as definitive treatment when definitive surgery is not feasible as postoperative adjuvant treatment and preoperatively in patients with a slow response to neoadjuvant chemotherapy Patients who are to receive definitive and postoperative adjuvant treatment are randomized between conventional fractionation and hyperfractionated accelerated split-course delivery individuals receiving preoperative irradiation are not randomized for radiotherapy schedule but are assigned nonrandomly to receive the hyperfractionated accelerated split-course scheme conventional fractionation requires that DOX and DACT be eliminated from concomitant chemotherapy whereas these agents can be continued during the hyperfractionated schedule Individual institutions may elect not to randomize for the radiotherapy fractionation scheme ie to treat all patients on one schedule or the other in such institutions all patients must follow the same scheme decided upon prior to treatment of the first patient Use of photons with energies of 4-6 MV including Co60 is recommended for extremity lesions and 6-15 MV energies are recommended for trunk lesions electrons may be considered for small superficial boosts but are not adequate as a sole modality ADJUVANT THERAPY Arm III Standard risk Alternating 3-Drug Combination Chemotherapy Regimens VACA VCRDOXCTX alternating with VCRDACTCTX Arm IV Standard risk Alternating 3-Drug Combination Chemotherapy Regimens VAIA VCRDOXIFF alternating with VCRDACTIFF High-risk patients continue with 10 additional courses of VAIA or EVAIA according to original randomization Adjuvant Radiotherapy when administered begins on week 19 and is given concomitantly with chemotherapy
PROJECTED ACCRUAL It is anticipated that 600 patients 200 standard-risk and 400 high-risk will be accrued over 4 years
OUTLINE Randomized study Patients are initially stratified as STANDARD RISK tumor volume at diagnosis 100 ml and HIGH RISK tumor volume at diagnosis at least 100 ml or if 100 ml metastasis present All patients receive 14 courses of chemotherapy administered q 3 weeks throughout protocol treatment Standard-risk patients receive 4 courses of NEOADJUVANT CHEMOTHERAPY on Regimen A while high-risk patients are randomized on Arms I and II for 4 courses of neoadjuvant chemotherapy LOCAL THERAPY is usually initiated on week 12 after 4 courses of neoadjuvant chemotherapy and consists of either total removal of the tumor-bearing compartment intracompartmental surgery with or without adjuvant radiotherapy or definitive radiotherapy alone the choice is dictated by the site tumor size and patient age among other variables Postoperatively all patients receive 10 courses of ADJUVANT CHEMOTHERAPY plus adjuvant radiotherapy when given standard-risk patients are randomized on Arms III and IV while high-risk patients receive the same regimen to which they were assigned at initial randomization When given adjuvant radiotherapy begins on week 19 and is administered concurrently with chemotherapy As a variant of this general plan patients with 50 regression of the soft tissue component of their tumors at restaging after 2 courses of neoadjuvant chemotherapy slow response may receive preoperative irradiation beginning on week 7 concomitantly with the third and fourth courses of chemotherapy The following acronyms are used CTX Cyclophosphamide NSC-26271 DACT Dactinomycin NSC-3053 DOX Doxorubicin NSC-123127 IFF Ifosfamide NSC-109724 Mesna Mercaptoethane sulfonate NSC-113891 VCR Vincristine NSC-67574 VP-16 Etoposide NSC-141540 NEOADJUVANT CHEMOTHERAPY Regimen A Standard risk Alternating 3-Drug Combination Chemotherapy Regimens VAIA VCRDOXIFF alternating with VCRDACTIFF Arm I High risk Alternating 3-Drug Combination Chemotherapy Regimens VAIA VCRDOXIFF alternating with VCRDACTIFF Arm II High-risk Alternating 4-Drug Combination Chemotherapy Regimens EVAIA VP-16VCRDOXIFF alternating with VP-16VCRDACTIFF LOCAL THERAPY Surgery Resection of entire tumor-bearing compartment including bone and soft tissue when possible is the treatment of choice The range of possible surgical procedures includes radical resection eg amputation wide resection en bloc removal of the entire tumor-bearing compartment marginal surgery en bloc removal but resection line runs through pseudocapsule and microscopic residual disease is likely intralesional resection tumor incised with contamination of surgical field and no resection Radiotherapy There are 3 settings in which radiotherapy is delivered in these patients as definitive treatment when definitive surgery is not feasible as postoperative adjuvant treatment and preoperatively in patients with a slow response to neoadjuvant chemotherapy Patients who are to receive definitive and postoperative adjuvant treatment are randomized between conventional fractionation and hyperfractionated accelerated split-course delivery individuals receiving preoperative irradiation are not randomized for radiotherapy schedule but are assigned nonrandomly to receive the hyperfractionated accelerated split-course scheme conventional fractionation requires that DOX and DACT be eliminated from concomitant chemotherapy whereas these agents can be continued during the hyperfractionated schedule Individual institutions may elect not to randomize for the radiotherapy fractionation scheme ie to treat all patients on one schedule or the other in such institutions all patients must follow the same scheme decided upon prior to treatment of the first patient Use of photons with energies of 4-6 MV including Co60 is recommended for extremity lesions and 6-15 MV energies are recommended for trunk lesions electrons may be considered for small superficial boosts but are not adequate as a sole modality ADJUVANT THERAPY Arm III Standard risk Alternating 3-Drug Combination Chemotherapy Regimens VACA VCRDOXCTX alternating with VCRDACTCTX Arm IV Standard risk Alternating 3-Drug Combination Chemotherapy Regimens VAIA VCRDOXIFF alternating with VCRDACTIFF High-risk patients continue with 10 additional courses of VAIA or EVAIA according to original randomization Adjuvant Radiotherapy when administered begins on week 19 and is given concomitantly with chemotherapy
PROJECTED ACCRUAL It is anticipated that 600 patients 200 standard-risk and 400 high-risk will be accrued over 4 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| UKCCSG-ET1993-02 | None | None | None |
| GER-GPOH-EICESS-92 | None | None | None |
| MRC-EICESS-92 | None | None | None |
| EU-92030 | None | None | None |
| EU-205116 | None | None | None |