Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01231906




Registration number
NCT01231906
Ethics application status
Date submitted
29/10/2010
Date registered
1/11/2010
Date last updated
31/08/2023

Titles & IDs
Public title
Combination Chemotherapy in Treating Patients With Non-Metastatic Extracranial Ewing Sarcoma
Scientific title
A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma
Secondary ID [1] 0 0
NCI-2011-02611
Secondary ID [2] 0 0
AEWS1031
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Localized Extraskeletal Ewing Sarcoma 0 0
Peripheral Primitive Neuroectodermal Tumor of Bone 0 0
Peripheral Primitive Neuroectodermal Tumor of Soft Tissues 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Dexrazoxane
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Drugs - Ifosfamide
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Topotecan Hydrochloride
Treatment: Drugs - Vincristine Sulfate

Experimental: Arm A (combination chemotherapy) - INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9, and 10; doxorubicin hydrochloride IV over 1-15 minutes (or as per institutional policies up to 60-minutes) on days 1 and 2 and cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 5, and 9; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 7, and 11.
CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7, 8, 9, 10, 13, 14, 17, 18, 21, and 22; doxorubicin hydrochloride IV on days 1 and 2 in weeks 1 and 9; cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 7, 9, 13, 17, and 21; and ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 5, 11, 15, and 19. Patients received Dexrazoxane with doxorubicin hydrochloride in weeks 1 and 9.

Experimental: Arm B (combination chemotherapy, topotecan hydrochloride) - INDUCTION THERAPY: Patients receive vincristine sulfate 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 15-30 minutes on days 1-5 in weeks 1 and 9, and over 30-60 minutes on day 1 of weeks 5 and 11; ifosfamide and etoposide as in arm A; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 5 and 11.
CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7-10, 13-16, 19, and 20; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1, 7, and 15; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1, 7, and 15, and over 30-60 minutes on day 1 in weeks 9, 13, and 19; ifosfamide IV over 1 hour and etoposide IV over 1- 2 hours on days 1-5 in weeks 3, 5, 11, 17, and 21; and doxorubicin hydrochloride IV on days 1 and 2 in weeks 9,13, and 19. Patients received Dexrazoxane with doxorubicin hydrochloride in weeks 13 and 19.


Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Dexrazoxane


Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Ifosfamide
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Topotecan Hydrochloride
Given IV

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event-Free Survival
Timepoint [1] 0 0
5 years after enrollment

Eligibility
Key inclusion criteria
- Patients with newly diagnosed, biopsy confirmed, extracranial, non-metastatic Ewing
sarcoma or primitive neuroectodermal tumor (PNET) of bone or soft tissue are eligible
for this study; note:

- For the purpose of this study, chest wall tumors with ipsilateral pleural
effusions, ipsilateral positive pleural fluid cytology or ipsilateral pleural
based secondary tumor nodules will be considered localized disease

- Patients with regional node involvement, based on clinical suspicion confirmed by
pathologic documentation are considered to be non-metastatic

- Patients with discontinuous osseous lesions within the same bone are considered
to be non-metastatic

- Tumors arising in the bony skull (extra-dural) are considered to be extracranial

- Patient eligibility will be based on a diagnosis of Ewing sarcoma or PNET by
institutional pathologist

- No prior chemotherapy or radiation therapy is allowed; patients should only have had a
biopsy of the primary tumor without an attempt at complete or partial resection;
patients will still be eligible if unplanned excision was attempted or accomplished as
long as adequate imaging was obtained prior to surgery

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70mL/min/1.73
m^2 or serum creatinine based on age/gender as follows:

- 1 month to < 6 months: 0.4 mg/dL

- 6 months to < 1 year: 0.5 mg/dL

- 1 to < 2 years: 0.6 mg/dL

- 2 to < 6 years: 0.8 mg/dL

- 6 to < 10 years: 1 mg/dL

- 10 to < 13 years: 1.2 mg/dL

- 13 to < 16 years: 1.5 mg/dL (male), 1.4 mg/dL (female)

- >= 16 years: 1.7 mg/dL (male), 1.4 mg/dL (female)

- Total bilirubin < 1.5 x upper limit of normal (ULN) for age

- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age

- Shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by
radionuclide angiogram
Minimum age
No limit
Maximum age
50 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients must have no evidence of metastatic disease; metastatic disease are lesions
which are discontinuous from the primary tumor, are not regional lymph nodes and do
not share a body cavity with the primary tumor; if there is any doubt whether lesions
are metastatic, a biopsy of those lesions should be taken

- Skeletal lesions in adjacent bones (trans-articular)

- Contralateral pleural effusion and contralateral pleural nodules

- Distant lymph node involvement

- Patients with pulmonary nodules are considered to have metastatic disease if the
patient has:

- Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied and
negative for Ewing's

- Biopsies of solitary nodule =< 0.5 cm or multiple nodules =< 0.3 cm are not
required but if performed and positive indicate metastatic disease

- Patients whose tumors arise in the dural and intra-dural soft tissues of the cranium
and spine are not eligible

- Patients with pathologic diagnoses other than Ewing sarcoma will be excluded

- Patients diagnosed with Ewing Sarcoma as a second malignant neoplasm are not eligible
if they have received chemotherapy or radiation for the treatment of their primary
malignancy

- Pregnant women will not be entered on this study; pregnancy tests must be obtained in
female patients who are post-menarchal; lactating females may not participate unless
they have agreed not to breastfeed their infants; males or females of reproductive
potential may not participate unless they have agreed to use an effective
contraceptive method for the duration of the study treatment

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
22/11/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
642
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [5] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [6] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [7] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [8] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
4101 - South Brisbane
Recruitment postcode(s) [6] 0 0
5006 - North Adelaide
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
State/province [3] 0 0
Arizona
Country [4] 0 0
United States of America
State/province [4] 0 0
Arkansas
Country [5] 0 0
United States of America
State/province [5] 0 0
California
Country [6] 0 0
United States of America
State/province [6] 0 0
Colorado
Country [7] 0 0
United States of America
State/province [7] 0 0
Connecticut
Country [8] 0 0
United States of America
State/province [8] 0 0
Delaware
Country [9] 0 0
United States of America
State/province [9] 0 0
District of Columbia
Country [10] 0 0
United States of America
State/province [10] 0 0
Florida
Country [11] 0 0
United States of America
State/province [11] 0 0
Georgia
Country [12] 0 0
United States of America
State/province [12] 0 0
Hawaii
Country [13] 0 0
United States of America
State/province [13] 0 0
Idaho
Country [14] 0 0
United States of America
State/province [14] 0 0
Illinois
Country [15] 0 0
United States of America
State/province [15] 0 0
Indiana
Country [16] 0 0
United States of America
State/province [16] 0 0
Iowa
Country [17] 0 0
United States of America
State/province [17] 0 0
Kentucky
Country [18] 0 0
United States of America
State/province [18] 0 0
Louisiana
Country [19] 0 0
United States of America
State/province [19] 0 0
Maine
Country [20] 0 0
United States of America
State/province [20] 0 0
Maryland
Country [21] 0 0
United States of America
State/province [21] 0 0
Massachusetts
Country [22] 0 0
United States of America
State/province [22] 0 0
Michigan
Country [23] 0 0
United States of America
State/province [23] 0 0
Minnesota
Country [24] 0 0
United States of America
State/province [24] 0 0
Mississippi
Country [25] 0 0
United States of America
State/province [25] 0 0
Missouri
Country [26] 0 0
United States of America
State/province [26] 0 0
Nebraska
Country [27] 0 0
United States of America
State/province [27] 0 0
Nevada
Country [28] 0 0
United States of America
State/province [28] 0 0
New Hampshire
Country [29] 0 0
United States of America
State/province [29] 0 0
New Jersey
Country [30] 0 0
United States of America
State/province [30] 0 0
New Mexico
Country [31] 0 0
United States of America
State/province [31] 0 0
New York
Country [32] 0 0
United States of America
State/province [32] 0 0
North Carolina
Country [33] 0 0
United States of America
State/province [33] 0 0
North Dakota
Country [34] 0 0
United States of America
State/province [34] 0 0
Ohio
Country [35] 0 0
United States of America
State/province [35] 0 0
Oklahoma
Country [36] 0 0
United States of America
State/province [36] 0 0
Oregon
Country [37] 0 0
United States of America
State/province [37] 0 0
Pennsylvania
Country [38] 0 0
United States of America
State/province [38] 0 0
Rhode Island
Country [39] 0 0
United States of America
State/province [39] 0 0
South Carolina
Country [40] 0 0
United States of America
State/province [40] 0 0
South Dakota
Country [41] 0 0
United States of America
State/province [41] 0 0
Tennessee
Country [42] 0 0
United States of America
State/province [42] 0 0
Texas
Country [43] 0 0
United States of America
State/province [43] 0 0
Utah
Country [44] 0 0
United States of America
State/province [44] 0 0
Vermont
Country [45] 0 0
United States of America
State/province [45] 0 0
Virginia
Country [46] 0 0
United States of America
State/province [46] 0 0
Washington
Country [47] 0 0
United States of America
State/province [47] 0 0
West Virginia
Country [48] 0 0
United States of America
State/province [48] 0 0
Wisconsin
Country [49] 0 0
Canada
State/province [49] 0 0
Alberta
Country [50] 0 0
Canada
State/province [50] 0 0
British Columbia
Country [51] 0 0
Canada
State/province [51] 0 0
Manitoba
Country [52] 0 0
Canada
State/province [52] 0 0
Newfoundland and Labrador
Country [53] 0 0
Canada
State/province [53] 0 0
Nova Scotia
Country [54] 0 0
Canada
State/province [54] 0 0
Ontario
Country [55] 0 0
Canada
State/province [55] 0 0
Quebec
Country [56] 0 0
Canada
State/province [56] 0 0
Saskatchewan
Country [57] 0 0
New Zealand
State/province [57] 0 0
Auckland
Country [58] 0 0
New Zealand
State/province [58] 0 0
Christchurch
Country [59] 0 0
Puerto Rico
State/province [59] 0 0
San Juan
Country [60] 0 0
Saudi Arabia
State/province [60] 0 0
Riyadh

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
This trial examined the outcome benefit to patients of adding a new chemotherapy drug
combination to the established treatment approach for patients with extracranial Ewing
sarcoma, that had not spread from the primary site to other places in the body. The trial
randomly assigned patients at the time of study entry to receive established standard
treatment with the following 5-drugs: vincristine sulfate, doxorubicin hydrochloride,
cyclophosphamide, ifosfamide and etoposide. The outcome for patients receiving the standard
5-drug combination was compared to the outcome for patients who received the same 5-drugs
with an additional drug, topotecan hydrochloride delivered in a novel combination with
vincristine sulfate and cyclophosphamide.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01231906
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Patrick J Leavey
Address 0 0
Children's Oncology Group
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

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01231906