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A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma


Phase 3
N/A
50 Years
Not Enrolling
Both
Sarcoma

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Trial Information

A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma


OBJECTIVES:

Primary

- Compare the event-free and overall survival of patients with newly diagnosed localized
Ewing's sarcoma treated with doxorubicin hydrochloride, cyclophosphamide, vincristine,
etoposide, and ifosfamide with vs without topotecan hydrochloride.

- Compare the side effects of these regimens in these patients.

Secondary

- Evaluate initial tumor size as a prognostic factor for event-free survival of these
patients.

- Evaluate histological response as a prognostic factor for event-free survival of these
patients.

- Continue evaluation of biologic markers both as related to prognosis and as eventual
therapeutic targets via encouraging concurrent enrollment on COG-AEWS02B1.

- Evaluate radiologic response by positron emission tomography as a prognostic factor for
event-free survival.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age
(≤ 17 vs ≥ 18 years of age) and primary tumor site (pelvic vs nonpelvic [including
extra-osseous Ewing's sarcoma]). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks 1-3,
7-9, and 13-15; doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks
1, 7, and 13; cyclophosphamide IV over 1 hour on day 1 in weeks 1, 7, and 13; and
ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 in weeks 4, 10, and
16. Patients undergo local therapy comprising surgical resection in approximately week
18 and/or radiotherapy beginning in approximately week 19. Patients then receive
vincristine as above in weeks 19-21, 28-30, 34-36, 40-42, and 46-51; dexrazoxane
hydrochloride IV over 15 minutes on days 1 and 2 and doxorubicin hydrochloride as above
in weeks 19 and 28; cyclophosphamide as above in weeks 19, 28, 34, 40, 46, and 49; and
ifosfamide and etoposide as above in weeks 22, 25, 31, 37, and 43.

- Arm II: Patients receive vincristine IV over 1 minute once a week on day 1 in weeks
1-3, 7-9, and 13-16; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1
and 13; cyclophosphamide IV over 30 minutes on days 1-5 in weeks 1 and 13 and IV over 1
hour on day 1 in weeks 7 and 16; ifosfamide IV over 1 hour and etoposide IV over 1 hour
on days 1-5 in weeks 4 and 10; and doxorubicin hydrochloride IV over 15 minutes on days
1 and 2 in weeks 7 and 16. Patients undergo local therapy comprising surgical resection
in approximately week 18 and/or radiotherapy beginning in approximately week 19.
Patients then receive vincristine as above in weeks 19-21, 28-33, 37-42, and 46-48;
topotecan hydrochloride as above in weeks 19, 31, and 40; cyclophosphamide IV over 30
minutes in weeks 19, 31, and 40 and IV over 1 hour in weeks 28, 37, and 46; ifosfamide
and etoposide as above in weeks 22, 25, 34, 43, and 49; dexrazoxane hydrochloride IV
over 15 minutes on days 1 and 2 in weeks 37 and 46; and doxorubicin hydrochloride as
above in weeks 28, 37, and 46.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 528 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically and cytologically confirmed extracranial Ewing's sarcoma or primitive
neuroectodermal tumor (PNET) of bone or soft tissue

- Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive
pleural fluid cytology, or ipsilateral pleural-based secondary tumor nodules
allowed

- Contralateral pleural effusions or pleural nodules are not eligible

- Tumor arising in the bony skull (extradural) are eligible

- Tumors arising in the intradural soft tissue are not eligible

- Newly diagnosed disease

- Only have had a biopsy of the primary tumor without an attempt at complete or
partial resection

- Prior attempted or accomplished unplanned excision allowed provided adequate
imaging was obtained prior to surgery AND resection considered incomplete and
further local control required

- No evidence of metastatic disease, defined as lesions discontinuous from the primary
tumor, are not regional lymph nodes, and do not share a body cavity with the primary
tumor

- No evidence of metastatic lung disease by CT scan

- One pulmonary nodule > 1 cm in diameter OR > 1 nodule > 0.5 cm in diameter are
considered evidence of pulmonary metastasis

- Solitary nodules 0.5-1.0 cm or multiple nodules 0.3-0.5 cm must be confirmed
negative by biopsy

- Solitary nodules < 0.5 cm or multiple nodules < 0.3 cm not considered clear
evidence of lung disease

- No distant nodule disease

- No esthesioneuroblastoma

PATIENT CHARACTERISTICS:

- Performance status (PS) 0-2 (Karnofsky PS 50-100% for patients ≥ 16 years of age or
Lansky PS 50-100% for patients < 16 years of age)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST or ALT < 2.5 times ULN

- Shortening fraction ≥ 27% by EKG

- Ejection fraction ≥ 50% by radionuclide angiogram

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radiotherapy

- No prior chemotherapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Safety Issue:

No

Principal Investigator

Mason Bond, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's & Women's Hospital of British Columbia

Authority:

Unspecified

Study ID:

AEWS0531

NCT ID:

NCT00334867

Start Date:

December 2005

Completion Date:

Related Keywords:

  • Sarcoma
  • localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma

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