A Pilot Study of Chemotherapy Intensification by Adding Vincristine, Topotecan and Cyclophosphamide to Standard Chemotherapy Agents With an Interval Compression Schedule in Newly Diagnosed Patients With Localized Ewing Sarcoma Family of Tumors
N/A
30 Years
Both
Ewing Sarcoma of Bone, Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Trial Information
A Pilot Study of Chemotherapy Intensification by Adding Vincristine, Topotecan and Cyclophosphamide to Standard Chemotherapy Agents With an Interval Compression Schedule in Newly Diagnosed Patients With Localized Ewing Sarcoma Family of Tumors
PRIMARY OBJECTIVES:
I. To assess the feasibility and safety of adding interval-compressed vincristine, topotecan
hydrochloride, and cyclophosphamide to a treatment protocol utilizing interval compression
of vincristine, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide in
patients with localized Ewing sarcoma family of tumors.
SECONDARY OBJECTIVES:
I. To estimate the event-free survival in patients treated with this regimen.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (WEEKS 1-12): Patients receive vincristine IV on day 1 in weeks 1, 2, 5,
6, 9, 10, 11, and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and
9; cyclophosphamide IV over 1 hour on days 1-5 in weeks 1 and 9 and on day 1 in weeks 5 and
11; ifosfamide IV over 1 hour on days 1-5 in weeks 3 and 7; etoposide IV over 1 hour on days
1-5 in weeks 3 and 7; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in
weeks 5 and 11. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning 24-36
hours after the last dose of chemotherapy and continuing for at least 7 days or until blood
counts recover, whichever comes last. Filgrastim is discontinued at least 24 hours prior to
the next course of chemotherapy.
LOCAL CONTROL: Patients who respond to induction therapy may undergo surgery alone if the
lesion can be resected with negative margins and with a reasonable functional result
beginning in week 13. Following surgery, patients with unresectable lesions or inadequate
margins may receive radiotherapy during week 15. Patients with bulky lesions in surgically
difficult sites such as the spine, skull, and periacetabular pelvis; poor response to
induction chemotherapy; or those in whom surgery would result in unacceptable functional
results may receive radiotherapy alone in weeks 13-19. Patients with bulky lesions in
difficult sites and who do not have a good clinical and radiographic response to induction
therapy may receive radiotherapy to the primary site during weeks 13-19 followed by surgery
of the involved site during week 25 after recovery from course 11 of chemotherapy. Patients
with microscopic residual disease after planned pre-operative radiotherapy will receive
additional radiotherapy.
CONTINUATION THERAPY (WEEKS 15-36): Patients receive vincristine IV on day 1 in weeks 15,
16, 21-24, 27-30, 33, and 34; topotecan hydrochloride IV over 30 minutes on days 1-5 in
weeks 15, 21, and 29; cyclophosphamide IV over 1 hour on days 1-5 in weeks 15, 21 and 29 and
on day 1 in weeks 23, 27, and 33; ifosfamide IV over 1 hour on days 1-5 in weeks 17, 19, 25,
31, and 35; etoposide IV over 1 hour on days 1-5 in weeks 17, 19, 25, 31, and 35; and
doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 of weeks 23, 27, and 33.
Patients also receive G-CSF SC as in induction therapy.
After completion of study treatment, patients are followed for 10 years.
Inclusion Criteria:
- Diagnosis of extracranial Ewing sarcoma or peripheral primitive neuroectodermal tumor
of bone or soft tissue:
- Newly diagnosed disease
- Disease confirmed by biopsy only with no attempt at complete or partial
resection
- Unplanned excision allowed provided adequate imaging was obtained prior to
surgery and incompletely resected disease is controlled by local therapy
- No esthesioneuroblastoma
- Localized disease, including any of the following sites:
- Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive
pleural fluid cytology, or ipsilateral pleural based secondary tumor nodules;
- No contralateral pleural effusions or pleural nodules
- Regional lymph nodes that are clinically suspicious or confirmed by biopsy
- No distant lymph node metastases
- Extra-dural tumors arising in the bony skull
- No tumors arising in the intra-dural soft tissue or the intra-dural region
of the spine
- No evidence of metastatic disease, defined as any of the following:
- Lesions that are discontinuous from the primary tumor
- Lesions that are not regional lymph nodes
- Lesions that do not share a body cavity with the primary tumor
- No evidence by CT scan of metastatic lung disease, defined as any of the following:
- One pulmonary nodule > 1 cm in diameter or more than one nodule > 0.5 cm
diameter
- Pulmonary nodules that are resected and are not found to be metastatic
Ewing sarcoma are allowed
- Biopsy proven solitary nodules measuring 0.5 to 1.0 cm or multiple nodules
measuring 0.3 to 0.5 cm
- Solitary nodules measuring < 0.5 cm or multiple nodules measuring < 0.3 cm
are allowed unless biopsy proven to be metastatic (biopsy is not required)
- Karnofsky performance status (PS) 0-2 (>= 16 years old) OR Lansky PS 0-2 (< 16 years
old)
- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
creatinine based on age/gender as follows:
- 1 month to < 6 months old (males and females 0.4 mg/dL)
- 6 months to < 1 year old (males and females 0.5 mg/dL)
- 1 to < 2 years old (males and females 0.6 mg/dL)
- 2 to < 6 years old (males and females 0.8 mg/dL)
- 6 to < 10 years old (males and females 1.0 mg/dL)
- 10 to < 13 years old (males and females 1.2 mg/dL)
- 13 to < 16 years old (males 1.5 mg/dL and females 1.4 mg/dL)
- >= 16 years old (males 1.7 mg/dL and females 1.4 mg/dL)
- AST or ALT < 2.5 times ULN for age
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- Shortening fraction of >= 27% by ECHO or ejection fraction of >= 50% by radionuclide
angiogram (MUGA)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior chemotherapy or radiotherapy
- No concurrent pegfilgrastim (Neulasta) or sargramostim (GM-CSF)
- No other concurrent cancer chemotherapy or immunomodulating agents, including
steroids, unless used as an antiemetic
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of death from complications during therapy or within one month of terminating therapy
Outcome Time Frame:
Up to 1 month
Safety Issue:
Yes
Principal Investigator
Leo Mascarenhas
Investigator Role:
Principal Investigator
Investigator Affiliation:
Children's Oncology Group
Authority:
United States: Food and Drug Administration
Study ID:
AEWS07P1
NCT ID:
NCT00618813
Start Date:
March 2008
Completion Date:
Related Keywords:
- Ewing Sarcoma of Bone
- Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
- Neuroectodermal Tumors
- Neuroectodermal Tumors, Primitive
- Sarcoma, Ewing's
- Neuroectodermal Tumors, Primitive, Peripheral
- Sarcoma
- Osteosarcoma
Name | Location |
|---|---|
| Children's Oncology Group | Arcadia, California 91006-3776 |
