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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00061893




Registration number
NCT00061893
Ethics application status
Date submitted
5/06/2003
Date registered
6/06/2003
Date last updated
15/02/2019

Titles & IDs
Public title
Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors
Scientific title
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
Secondary ID [1] 0 0
CDR0000302409
Secondary ID [2] 0 0
AEWS02P1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - celecoxib
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - ifosfamide
Treatment: Drugs - vinblastine sulfate
Treatment: Drugs - vincristine sulfate
Treatment: Surgery - conventional surgery
Treatment: Other - radiation therapy
Treatment: Drugs - MESNA
Treatment: Drugs - Filgrastim

Experimental: Combination chemotherapy - Metastatic Ewing Sarcoma - 14-cycle study building on conventional tx (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, ifosfamide, etoposide) and adding two antiangiogenic agents: the vinca alkaloid vinblastine and the cyclooxygenase-2 inhibitor celecoxib. Refer to the Interventions section for dosages, method of delivery and frequency of administration.


Treatment: Drugs: celecoxib
Given orally, Celecoxib 250 mg/m2 PO BID (500mg/m2/day) from Day 1 of Cycle 1 through Day 21 of Cycle 14. The dose should be rounded off to the nearest 100 mg. If PK studies are being done, Celecoxib should be given 24 hours prior to the other drugs for Cycle 1 only. [Celecoxib may be interrupted for up to 7 days around the time of surgical procedures.] .

Treatment: Drugs: cyclophosphamide
Given IV, 1200 mg/m2 IV infusion over 1 hour with MESNA uroprotection, on Day 1. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.

Treatment: Drugs: doxorubicin hydrochloride
Given IV, Doxorubicin 75 mg/ m2 /course continuous IV infusion over 48 hours, beginning Day 1. Note: The total doxorubicin dose per cycle is 75 mg/ m2, which will be given as 37.5 mg/m2/day x 2 days. Doxorubicin may be given as a continuous infusion or brief infusion.

Treatment: Drugs: etoposide
Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.

Treatment: Drugs: ifosfamide
Given IV,Ifosfamide 1800 mg/m2 /day IV infusion over 1 hour, Days 1-5 of each cycle. (9,000 mg/m2 max total dose per cycle). Prehydrate for 6 hours, 1,000 ml/m2 total volume (165 ml/m2/hour for 6 hours). For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.

Treatment: Drugs: vinblastine sulfate
Given IV, Vinblastine 1 mg/m2/d IV push three times per week beginning Day 1 of Cycle 1 and continuing through Day 21 of Cycle 14. In weeks during which vincristine is given, hold one dose of vinblastine and administer only 2 doses of vinblastine during that week. If vinblastine is due the same day as vincristine, hold that dose of vinblastine. [Vinblastine may be interrupted for up to 7 days around the time of surgical procedures.]

Treatment: Drugs: vincristine sulfate
Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.

Treatment: Surgery: conventional surgery
Patients who respond to induction chemotherapy undergo surgery on week 13. Patients who have inadequate margins after surgery undergo radiotherapy beginning on week 15. (see Detailed Description for frequency of administration and groups evaluated)

Treatment: Other: radiation therapy
Patients with unresectable lesions undergo radiotherapy 5 days a week for approximately 6 weeks beginning on week 13. (see Detailed Description for frequency of administration and groups evaluated)

Treatment: Drugs: MESNA
The total daily MESNA dose is equal to at least 60% of the daily cyclophosphamide or ifosfamide dose, or by continuous infusion of the 60% dose. MESNA continuous infusion should be started at the same time as the cyclophosphamide/ifosfamide and be completed no sooner than 8 hours after the end of the cyclophosphamide or ifosfamide infusion. The oral dose of MESNA is 2x the IV dose. Patients able to tolerate oral MESNA may receive the final dose by mouth at 40% of the oxazaphosphorine (cyclophosphamide or ifosfamide) dose. The dose should be given two hours earlier than the IV dose would be given. Additionally, if the patient vomits within two hours after the oral dose, the dose should be repeated or IV MESNA given.

Treatment: Drugs: Filgrastim
G-CSF (Filgrastim) 5 micrograms/kg/day subcutaneously beginning 24 to 48 hours after the last dose of chemotherapy, and continuing until the absolute neutrophil count is 2,000/µL or greater after nadir.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Occurrence of Severe Toxicity - 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.
Timepoint [1] 0 0
The first two cycles (6 weeks) of protocol chemotherapy
Secondary outcome [1] 0 0
Event Free Survival
Timepoint [1] 0 0
24 months after start of protocol therapy

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- 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
eligible

- 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

PATIENT CHARACTERISTICS:

Age

- 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

Hematopoietic

- Not specified

Hepatic

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

- AST or ALT less than 5 times ULN

Renal

- 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)

Cardiovascular

- Shortening fraction at least 27% by echocardiogram OR

- Ejection fraction at least 50% by MUGA

Other

- 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior bone marrow or stem cell transplantation

Chemotherapy

- No prior chemotherapy

Endocrine therapy

- Not specified

Radiotherapy

- No prior radiotherapy

Surgery

- Not specified

Other

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

- No concurrent dexrazoxane unless approved by the study investigator
Minimum age
No limit
Maximum age
50 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Institute for Cancer Research at Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
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Alabama
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Kentucky
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Maine
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Missouri
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Nevada
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New Jersey
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New York
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North Carolina
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Oregon
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Pennsylvania
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South Carolina
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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West Virginia
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Wisconsin
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Alberta
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British Columbia
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Manitoba
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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Puerto Rico
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Santurce

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
RATIONALE: Drugs used in chemotherapy, such as vinblastine, work in different ways to stop
tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of
Ewing's sarcoma by stopping blood flow to the tumor. Combining more than one chemotherapy
drug with celecoxib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining low-dose vinblastine and
celecoxib with standard regimens of combination chemotherapy in treating patients who have
newly-diagnosed metastatic Ewing's sarcoma family of tumors.
Trial website
https://clinicaltrials.gov/show/NCT00061893
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Judy L. Felgenhauer, MD, PS
Address 0 0
Sacred Heart Children's Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications