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A Pilot Study of Low-Dose Antiangiogenic Chemotherapy in Combination With Standard Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma Family of Tumors

Phase 2
50 Years
Not Enrolling

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Trial Information

A Pilot Study of Low-Dose Antiangiogenic Chemotherapy in Combination With Standard Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma Family of Tumors


- Determine the feasibility and safety of low-dose vinblastine and celecoxib in
combination with standard multiagent chemotherapy in patients with newly diagnosed
metastatic Ewing's sarcoma family of tumors.

- Determine the event-free survival of patients treated with this regimen.

- Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a pilot, multicenter study.

- Induction therapy: Patients receive the following alternating regimens:

- VAC (courses 1 and 3): Patients receive vincristine IV and cyclophosphamide IV
over 1 hour on day 1 and doxorubicin IV continuously on days 1 and 2 of weeks 1
and 7.

- IE (courses 2 and 4): Patients receive ifosfamide IV over 1 hour and etoposide IV
over 1-2 hours on days 1-5 of weeks 4 and 10.

Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning 24-48 hours after the
last dose of chemotherapy and continuing until blood counts recover.

Treatment repeats every 21 days for a total of 4 courses in the absence of disease
progression or unacceptable toxicity.

- Local control and consolidation therapy: Beginning on week 13, patients are assigned to
1 of 4 regimens based on disease status.

- Regimen A (surgery only): Patients who respond to induction chemotherapy undergo
surgery on week 13. Patients then begin consolidation therapy on week 15 with the
following alternating regimens:

- VAC (courses 5, 7, and 9): Patients receive VAC on weeks 15, 21, and 27.

- IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 18, 24, 30,
36, and 42.

- VC (courses 11 and 13): Patients receive vincristine IV and cyclophosphamide
IV over 1 hour on weeks 33 and 39.

- Regimen B (radiotherapy only): Patients with unresectable lesions undergo
radiotherapy once daily 5 days a week for up to approximately 6 weeks beginning on
week 13. Patients also receive consolidation therapy beginning on week 13, with
the following alternating regimens:

- VAC (courses 5, 9, and 11): Patients receive VAC on weeks 13, 25, and 31.

- IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 16, 22, 28,
34, and 40.

- VC (courses 7 and 13): Patients receive VC on weeks 19 and 37.

- Regimen C (surgery and radiotherapy): Patients who respond to induction
chemotherapy undergo surgery on week 13. Patients who have inadequate margins
after surgery undergo radiotherapy (as in regimen B) beginning on week 15.
Patients also receive consolidation therapy, beginning on week 15, with the
following alternating regimens:

- VAC (courses 5, 9, and 11): Patients receive VAC on weeks 15, 27, and 33.

- IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 18, 24, 30,
36, and 42.

- VC (courses 7 and 13): Patients receive VC on weeks 21 and 39.

- Regimen D (preoperative radiotherapy): Patients with bulky lesions who do not have
a good clinical and radiographic response to induction therapy begin consolidation
therapy on week 13 with VAC (course 5) and undergo concurrent radiotherapy as in
regimen B. Patients then receive IE on weeks 16 and 19 for courses 6 and 7.
Patients undergo surgery on week 22. Patients continue consolidation therapy with
the following alternating regimens:

- VAC (courses 8 and 9): Patients receive VAC on weeks 24 and 27.

- IE (courses 10, 12, and 14): Patients receive IE on weeks 30, 36, and 42.

- VC (courses 11 and 13): Patients receive VC on weeks 33 and 39. Patients
receive G-CSF SC (as in induction therapy) during all consolidation courses.

Consolidation therapy continues for 10 courses in the absence of disease progression or
unacceptable toxicity.

- Vinblastine and celecoxib therapy: Throughout induction, local control, and
consolidation therapies, patients also receive vinblastine IV 3 times a week (twice a
week during the weeks that vincristine is given) and oral celecoxib twice daily,
beginning on day 1 of course 1 and continuing until the completion of course 14.* NOTE:
*To assess for safety, the first 6 patients enrolled receive vinblastine only during
courses 1 and 2 and celecoxib is then added for all subsequent courses.

Patients are followed every 3 months for 3 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 6-36 patients will be accrued for this study within 1.17

Inclusion Criteria


- Newly diagnosed Ewing's sarcoma family of tumors of the bone or soft tissues

- Paraspinal tumors of extra-dural origin and Askin's tumor of the chest wall are

- Metastatic disease, defined by the following criteria:

- Lesions are discontinuous from the primary tumor, are not regional lymph nodes,
and do not share a body cavity with the primary tumor

- A single pulmonary or pleural nodule greater than 1 cm OR multiple nodules
greater than 0.5 cm are considered evidence of pulmonary or pleural metastases
(unless there is another clear medical explanation for these lesions)

- Contralateral pleural effusions are considered metastatic disease

- No CNS involvement



- 50 and under (at diagnosis)

Performance status

- Lansky 50-100% (under 17 years of age)

- Karnofsky 50-100% (age 17 and over)

- Patients whose performance status is affected by a pathological fracture are
allowed provided they are able to undergo treatment

Life expectancy

- Not specified


- Not specified


- Bilirubin no greater than 1.5 times upper limit of normal (ULN)

- AST or ALT less than 5 times ULN


- Creatinine adjusted according to age as follows*:

- No greater than 0.4 mg/dL (≤ 5 months)

- No greater than 0.5 mg/dL (6 months -11 months)

- No greater than 0.6 mg/dL (1 year-23 months)

- No greater than 0.8 mg/dL (2 years-5 years)

- No greater than 1.0 mg/dL (6 years-9 years)

- No greater than 1.2 mg/dL (10 years-12 years)

- No greater than 1.4 mg/dL (13 years and over [female])

- No greater than 1.5 mg/dL (13 years to 15 years [male])

- No greater than 1.7 mg/dL (16 years and over [male]) OR

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min*
NOTE: *Unless these values are related to renal insufficiency secondary to tumor
involvement that is expected to improve once the tumor mass is smaller (e.g., pelvic
mass causing obstructive hydronephrosis)


- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA


- Not pregnant or nursing

- Fertile patients must use effective contraception

- Body surface area at least 0.4 m^2

- No allergy to sulfa

- No aspirin hypersensitivity

- No asthma triad (asthma with nasal polyps, and urticaria)

- No other prior cancer, including nonmelanoma skin cancer


Biologic therapy

- No prior bone marrow or stem cell transplantation


- No prior chemotherapy

Endocrine therapy

- Not specified


- No prior radiotherapy


- Not specified


- No other concurrent nonsteroidal anti-inflammatory medications, including salicylates

- No concurrent dexrazoxane unless approved by the study investigator

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Occurrence of Severe Toxicity

Outcome Description:

An incidence of severe toxicity is defined to be the occurrence of grade 3 or higher infection or grade 3 or higher sensory neuropathy during cycles 1-2 of protocol therapy. If 12 or more patients experience grade 3 or higher infection or five or more patients experience grade 3 or higher sensory neuropathy during cycles 1-2 of protocol therapy, the regimen will be flagged as being associated with an excessive rate of severe toxicity.

Outcome Time Frame:

Duration of Protocol Therapy

Safety Issue:


Principal Investigator

Judy L. Felgenhauer, MD, PS

Investigator Role:

Study Chair

Investigator Affiliation:

Sacred Heart Children's Hospital


United States: Federal Government

Study ID:




Start Date:

April 2004

Completion Date:

April 2008

Related Keywords:

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



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