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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00346164




Registration number
NCT00346164
Ethics application status
Date submitted
28/06/2006
Date registered
29/06/2006
Date last updated
6/10/2017

Titles & IDs
Public title
Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma
Scientific title
Risk-Based Treatment for Non-Rhabdomyosarcoma Soft Tissue Sarcomas (NRSTS) in Patients Under 30 Years of Age
Secondary ID [1] 0 0
NCI-2009-00426
Secondary ID [2] 0 0
ARST0332
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Alveolar Soft-part Sarcoma 0 0
Adult Angiosarcoma 0 0
Adult Epithelioid Sarcoma 0 0
Adult Extraskeletal Chondrosarcoma 0 0
Adult Extraskeletal Osteosarcoma 0 0
Adult Fibrosarcoma 0 0
Adult Leiomyosarcoma 0 0
Adult Liposarcoma 0 0
Adult Malignant Fibrous Histiocytoma 0 0
Adult Malignant Hemangiopericytoma 0 0
Adult Malignant Mesenchymoma 0 0
Adult Neurofibrosarcoma 0 0
Adult Synovial Sarcoma 0 0
Childhood Alveolar Soft-part Sarcoma 0 0
Childhood Angiosarcoma 0 0
Childhood Epithelioid Sarcoma 0 0
Childhood Fibrosarcoma 0 0
Childhood Leiomyosarcoma 0 0
Childhood Liposarcoma 0 0
Childhood Malignant Mesenchymoma 0 0
Childhood Neurofibrosarcoma 0 0
Childhood Synovial Sarcoma 0 0
Dermatofibrosarcoma Protuberans 0 0
Metastatic Childhood Soft Tissue Sarcoma 0 0
Nonmetastatic Childhood Soft Tissue Sarcoma 0 0
Stage I Adult Soft Tissue Sarcoma 0 0
Stage II Adult Soft Tissue Sarcoma 0 0
Stage III Adult Soft Tissue Sarcoma 0 0
Stage IV Adult Soft Tissue Sarcoma 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
Other cancer types
Neurological 0 0 0 0
Other neurological disorders
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - doxorubicin hydrochloride
Other interventions - clinical observation
Treatment: Surgery - therapeutic conventional surgery
Treatment: Other - 3-dimensional conformal radiation therapy
Treatment: Drugs - ifosfamide

Experimental: Arm A: No adjuvant treatment - Patients with low-grade tumor with either negative or positive microscopic margins or high-grade tumor = 5 cm (in maximum diameter) with negative microscopic margins are assigned to arm A: (observation only).

Experimental: Arm B: Low risk; adjuvant radiotherapy - Patients with high-grade tumor = 5 cm (in maximum diameter) with positive microscopic margins are assigned to arm B: (adjuvant radiotherapy). Beginning between 6-42 days after surgical resection, patients undergo a total of 31 fractions of adjuvant radiotherapy.

Experimental: Arm C: Intermediate & High risk; adjuvant chemoradiotherapy - High risk [metastatic, resected, incompletely resected, or unresected disease] patients with high-grade, grossly resected primary tumor, with metastases are assigned to receive arm C: (adjuvant chemoradiotherapy). Patients receive ifosfamide IV; doxorubicin hydrochloride IV; beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy.

Experimental: Arm D: Intermediate & High Risk; Neoadjuvant chemoradiotherapy - High risk [metastatic, resected, incompletely resected, or unresected disease] patients with unresected, high-grade metastatic tumor are assigned to receive treatment as in arm D: (neoadjuvant chemoradiotherapy, surgery, and adjuvant chemotherapy with or without radiotherapy): Patients receive ifosfamide IV; doxorubicin hydrochloride IV. Beginning in week 4, patients also undergo a total of 31 fractions of radiotherapy. Patients undergo surgical resection in week 13.


Treatment: Drugs: doxorubicin hydrochloride
Given IV

Other interventions: clinical observation
Patients undergo observation

Treatment: Surgery: therapeutic conventional surgery
Patients undergo surgery

Treatment: Other: 3-dimensional conformal radiation therapy
Patients undergo radiotherapy

Treatment: Drugs: ifosfamide
Given IV

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Surgery
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Probability for Event Free Survival. - Probability of no relapse, secondary malignancy or death after 5 years since enrollment.
Timepoint [1] 0 0
5 years
Secondary outcome [1] 0 0
Toxicity Rate - Percentage of Arm D patients experiencing grade 4+ adverse events.
Timepoint [1] 0 0
13 weeks
Secondary outcome [2] 0 0
Complete or Partial Response Rate - Tumor response by imaging. Complete Response (CR): Complete disappearance of the tumor. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment. Overall Response (OR)=CR+PR.
Timepoint [2] 0 0
13 weeks
Secondary outcome [3] 0 0
Percent Tumor Necrosis - Percent tumor necrosis by pathology review.
Timepoint [3] 0 0
13 weeks
Secondary outcome [4] 0 0
Event Free Survival Probability Disease Extent - Probability of no relapse, secondary malignancy or death after 5 years since enrollment.
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Event Free Survival Probability Histologic Grade - Probability of no relapse, secondary malignancy or death after 5 years since enrollment
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Overall Survival Probability Disease Extent - Probability of survival after 5 years since enrollment.
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Overall Survival Probability Extent of Resection of the Primary Tumor - Probability of survival after 5 years since enrollment.
Timepoint [7] 0 0
5 years
Secondary outcome [8] 0 0
Incidence of Distant Metastasis - Percent of patients who had distant metastasis.
Timepoint [8] 0 0
Up to 10 years
Secondary outcome [9] 0 0
Genetic and Gene Expression Profiles - The tumors from patients registered on D9902 will be analyzed for genetic and gene expression profiles. The study will prospectively evaluate each tumor and confirm newly defined sarcoma diagnostic criteria based on cancer signatures in NRSTS.
Timepoint [9] 0 0
At diagnosis
Secondary outcome [10] 0 0
Degree of Agreement in Histologic Grade Determined by the Enrolling Institution Versus by Central Pathology Reviewers - Histologic grades were determined by the central pathology reviewers and institutional pathologists based on published standards. A higher grade is associated with a more severe disease.
Timepoint [10] 0 0
At Diagnosis
Secondary outcome [11] 0 0
Degree of Agreement in Histologic Grade Between Pediatric Oncology Group (POG) and Fédération Nationale Des Centres de Lutte Contre le Cancer (FNCLCC) Pathologic Grading Systems - POG and FNCLCC grades were determined by pathologists based on published standards. A higher grade is associated with a more severe disease.
Timepoint [11] 0 0
At diagnosis

Eligibility
Key inclusion criteria
- Newly diagnosed non-rhabdomyosarcoma soft tissue sarcoma (STS), confirmed by central
pathology review via concurrent enrollment on protocol COG-D9902

- Metastatic or non metastatic disease

- Meets 1 of the following criteria:

- Intermediate (i.e., rarely metastasizing) or malignant STS, including any of the
following:

- Adipocytic tumor, including liposarcoma of any of the following histology
subtypes:

- Dedifferentiated

- Myxoid

- Round cell

- Pleomorphic type

- Mixed-type

- Not otherwise specified (NOS)

- Fibroblastic/myofibroblastic tumors, including any of the following:

- Solitary fibrous tumor

- Hemangiopericytoma

- Low-grade myofibroblastic sarcoma

- Myxoinflammatory fibroblastic sarcoma

- Adult fibrosarcoma*

- Myxofibrosarcoma

- Low-grade fibromyxoid sarcoma or hyalinizing spindle-cell tumor

- Sclerosing epithelioid fibrosarcoma

- So-called fibrohistiocytic tumors, including any of the following:

- Plexiform fibrohistiocytic tumor

- Giant cell tumor of soft tissues

- Pleomorphic malignant fibrous histiocytoma (MFH)/undifferentiated
pleomorphic sarcoma

- Giant cell MFH/undifferentiated pleomorphic sarcoma with giant cells

- Inflammatory MFH/undifferentiated pleomorphic sarcoma with prominent
inflammation

- Smooth muscle tumor (leiomyosarcoma)

- Pericytic [perivascular] tumor (malignant glomus tumor or glomangiosarcoma)

- Vascular tumor, including angiosarcoma

- Chondro-osseous tumors of any of the following types:

- Mesenchymal chondrosarcoma

- Extraskeletal osteosarcoma

- Tumors of uncertain differentiation, including any of the following:

- Angiomatoid fibrous histiocytoma

- Ossifying fibromyxoid tumor

- Myoepithelioma/parachordoma

- Synovial sarcoma

- Epithelioid sarcoma

- Alveolar soft-part sarcoma

- Clear cell sarcoma of soft tissue

- Extraskeletal myxoid chondrosarcoma ("chordoid type")

- Malignant mesenchymoma

- Neoplasms with perivascular epithelioid cell differentiation (PEComa)

- Clear cell myomelanocytic tumor

- Intimal sarcoma

- Malignant peripheral nerve sheath tumor

- Dermatofibrosarcoma protuberans meeting both of the following criteria:

- Non metastatic disease

- Tumor must be grossly resected prior to study enrollment

- Embryonal sarcoma of the liver

- Unclassified STS that is too undifferentiated to be placed in a specific
pathologic category (undifferentiated STS or STS NOS)

- Gross resection of the primary tumor = 42 days prior to enrollment required except if
any of the following circumstances apply:

- Non metastatic high-grade tumor > 5 cm in maximal diameter and gross or
microscopic residual tumor is anticipated after resection

- Tumor of either high- or- low-grade that cannot be grossly excised without
unacceptable morbidity

- High-grade tumor with metastases

- Patients with metastatic low-grade tumor whose disease is amenable to gross
resection at all sites must undergo gross resection of all sites prior to
study entry

- Patients with a tumor recurrence after a gross total resection are not eligible

- Tumors arising in bone are not eligible

- Patients with epithelioid sarcoma, clear cell sarcoma, or clinical or radiologic
evidence of regional lymph node enlargement must undergo sentinel lymph node biopsies
or lymph node sampling to confirm the status of regional lymph nodes* NOTE: *Except in
cases where the study radiologist reviews the imaging and indicates that a biopsy is
not needed to confirm that the patient has lymph node involvement.

- If lymph node biopsies are positive for tumor (or the lymph nodes are classified
as positive by the study radiologist), formal lymph node dissection must be done
at the time of definitive surgery(prior to study entry for patients assigned to
study regimen C)

- Patients with metastatic disease must undergo a biopsy to confirm the presence of
metastatic tumor if all metastases are < 1 cm in maximal diameter (except in cases
where the study radiologist reviews the imaging and indicated that a biopsy is not
needed to confirm that the patient has metastatic disease)

- Lansky performance status (PS) 50-100% (for patients = 16 years of age) OR Karnofsky
PS 50-100% (for patients > 16 years of age)

- Life expectancy = 3 months

- Absolute neutrophil count = 1,000/mm³*

- Platelet count = 100,000/mm³*

- Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min (= 40
mL/min for infants < 1 year of age)* or serum creatinine based on age and/or gender as
follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 year to < 2 years of age)

- 0.8 mg/dL (2 years to < 6 years of age)

- 1.0 mg/dL (6 years to < 10 years of age)

- 1.2 mg/dL (10 years to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (= 16 years of age)

- Patients with urinary tract obstruction by tumor must meet the renal function criteria
listed above AND must have unimpeded urinary flow established via decompression of the
obstructed portion of the urinary tract

- Bilirubin = 1.5 times upper limit of normal (ULN)*

- Shortening fraction = 27% by echocardiogram* OR ejection fraction = 50% by
radionuclide angiogram*

- Not pregnant or nursing (patients undergoing radiotherapy and/or chemotherapy)

- No nursing for = 1 month after completion of study treatment in study regimens C
or D

- Fertile patients must use effective contraception during and for = 1 month after
completion of study treatment

- Negative pregnancy test

- No evidence of dyspnea at rest*

- No exercise intolerance*

- Resting pulse oximetry reading > 94% on room air (for patients with respiratory
symptoms)*

- Prior treatment for cancer allowed provided the patient meet the prior therapy
requirements

- No prior anthracycline (e.g., doxorubicin or daunorubicin) or ifosfamide chemotherapy
for patients enrolled on arm C or arm D

- No prior radiotherapy to tumor-involved sites
Minimum age
No limit
Maximum age
29 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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
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,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Sydney
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [5] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [6] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 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
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Arizona
Country [3] 0 0
United States of America
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Arkansas
Country [4] 0 0
United States of America
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California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
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Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
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District of Columbia
Country [9] 0 0
United States of America
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Florida
Country [10] 0 0
United States of America
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Georgia
Country [11] 0 0
United States of America
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Hawaii
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Idaho
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Illinois
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United States of America
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Indiana
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Iowa
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United States of America
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
Country [22] 0 0
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Minnesota
Country [23] 0 0
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Mississippi
Country [24] 0 0
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Missouri
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New Mexico
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New York
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United States of America
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North Carolina
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United States of America
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North Dakota
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United States of America
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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United States of America
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [48] 0 0
Alberta
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Canada
State/province [49] 0 0
British Columbia
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Canada
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Manitoba
Country [51] 0 0
Canada
State/province [51] 0 0
Newfoundland and Labrador
Country [52] 0 0
Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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New Zealand
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Auckland
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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
This phase III trial is studying observation to see how well a risk based treatment strategy
works in patients with soft tissue sarcoma. In the study, patients are assigned to receive
surgery +/- radiotherapy +/- chemotherapy depending on their risk of recurrence. Sometimes,
after surgery, the tumor may not need additional treatment until it progresses. In this case,
observation may be sufficient. Radiation therapy uses high-energy x-rays to kill tumor cells.
Drugs used in chemotherapy, such as ifosfamide and doxorubicin, work in different ways to
stop the growth of tumor cells, either by killing the cells or by stopping them from
dividing. Giving chemotherapy and radiation therapy before surgery may make the tumor smaller
and reduce the amount of normal tissue that needs to be removed. Giving these treatments
after surgery may kill any tumor cells that remain after surgery.
Trial website
https://clinicaltrials.gov/show/NCT00346164
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sheri Spunt, MD
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
Other publications