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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00354744




Registration number
NCT00354744
Ethics application status
Date submitted
19/07/2006
Date registered
20/07/2006
Date last updated
29/01/2020

Titles & IDs
Public title
High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma
Scientific title
Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) for Patients With High-Risk Rhabdomyosarcoma
Secondary ID [1] 0 0
CDR0000489215
Secondary ID [2] 0 0
ARST0431
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
Cancer 0 0 0 0
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - dactinomycin
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - etoposide
Treatment: Drugs - ifosfamide
Treatment: Drugs - irinotecan hydrochloride
Treatment: Drugs - vincristine sulfate
Treatment: Surgery - conventional surgery
Treatment: Other - radiation therapy
Other interventions - filgrastim

Experimental: High Risk Rhabdomyosarcoma - Parameningeal (without intracranial extension) and paraspinal tumors receive chemotherapy starting Week 1 and begin radiation therapy at Week 20. Weeks 1-6: vincristine sulfate and irinotecan hydrochloride. Weeks 7-34: vincristine sulfate and irinotecan hydrochloride, Cyclophosphamide with MESNA, Doxorubicin hydrochloride, Etoposide, Ifosfamide with MESNA. Weeks 35-54: vincristine sulfate, Dactinomycin, irinotecan hydrochloride and Cyclophosphamide with MESNA and Filgrastim. Radiation therapy beginning at Week 20. Second look conventional surgery: Surgical resection other than biopsy will be applicable for the majority of patients.


Other interventions: dactinomycin
Age based dosage: = 1 year 0.045 mg/kg IV x 1(maximum dose 2.5 mg), < 1 year 0.025 mg/kg.
Day 1 of Weeks 35, 38, 41 and 44.
Given IV

Treatment: Drugs: cyclophosphamide
Age based dosage: = 3 years 1200 mg/m2, <3 years 40 mg/kg.
Day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41 and 44.
Given IV

Treatment: Drugs: doxorubicin hydrochloride
Age based dosage: = 1 year: 37.5mg/m²/day, < 1 year: treat with 50% doses calculated on a m2 basis. Total dose 75 mg/m².
Days 1 and 2 of weeks 7, 11, 15, 28 and 32.
Given IV

Treatment: Drugs: etoposide
Age based dosage: = 1 year: 100 mg/m²/day, < 1 year: treat with 50% doses calculated on a m2 basis.
Days 1-5 of weeks 9, 13, 17, 26 and 30.
Given IV

Treatment: Drugs: ifosfamide
Age based dosage: = 1 year: 1800 mg/m²/day, < 1 year: treat with 50% doses calculated on a m2 basis.
Days 1-5 of weeks 9, 13, 17, 26 and 30.
Given IV

Treatment: Drugs: irinotecan hydrochloride
Dosage 50 mg/m2-max dose 100 mg/day.
Days 1-5 of weeks 1, 4, 20, 23, 47 and 50.
Given IV

Treatment: Drugs: vincristine sulfate
Age based dosage: = 3 years 1.5 mg/m2 (max dose 2 mg), = 1 year and < 3 years 0.05 mg/kg (max dose 2 mg), < 1 year 0.025 mg/kg.
Days 1-5 of weeks 1, 2, 3, 4, 5, 7, 8, 11, 12, 15, 16, 20, 21, 22, 23, 24, 28, 29, 32, 33, 35, 38, 41, 42, 43, 44, 47, 48, 50, and 51.
Given IV

Treatment: Surgery: conventional surgery
Resection of the primary tumor with a surrounding "envelope" of normal tissue

Treatment: Other: radiation therapy
Radiotherapy beginning at Week 20 to the primary tumor and to the metastatic sites excepting those with parameningeal tumors with intracranial extension (direct extension into the brain) and those requiring emergency radiotherapy

Other interventions: filgrastim
5 micrograms/kg/day (max 300 micrograms) beginning 24-36 hours after the last dose of chemotherapy. Continue at least 7 days, or until the ANC =750/µL whichever comes last.
Given subcutaneously.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
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
Number of Patients With Complete or Partial Response Assessed by RECIST Criteria - Volumetric measurements of the primary tumor using an elliptical model (0.5 x the product of the 3 largest perpendicular diameters) to assess response to neoadjuvant therapy. The RECIST (Response Evaluation Criteria in Solid Tumors) from the NCI will be used for assessment of the size of measurable metastases, including nodal metastases. Primary Tumor Measurement: Technical guidelines for cross-sectional imaging computed tomography (CT) slice thickness should be 5mm or less and the diameter of the "measurable" mass should be at least twice the reconstructed slice thickness. Smaller masses are considered detectable, but will be counted as "non-measurable." Complete Response (CR): Complete disappearance of the tumor confirmed at >4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment. Progressive Disease (PD): At least 40% increase in tumor volume compared to the smallest volume obtained since the beginning.
Timepoint [1] 0 0
Protocol week 6 evaluation
Primary outcome [2] 0 0
Percentage of Patients Experiencing Adverse Events Due to Concurrent Therapy - Adverse events are reported for patients receiving concurrent irinotecan hydrochloride and radiotherapy.
Timepoint [2] 0 0
From enrollment to up to 2 years
Secondary outcome [1] 0 0
Percentage of Patients Event Free at 4 Years Following Study Entry - Event-free survival: Time to recurrence, second malignancy, or death as a first event, estimated from a Kaplan Meier curve
Timepoint [1] 0 0
4 years

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Histologically confirmed high-risk rhabdomyosarcoma or ectomesenchymoma

- Prior enrollment on COG-D9902 to confirm local histological diagnosis required

- Tissue must be submitted for pathologic review within 2 days of patient
registration on COG-D9902

- Newly diagnosed disease

- Metastatic disease (stage IV, clinical group IV)

- Has undergone initial surgical procedure (including biopsy) that provided the
definitive diagnosis within the past 42 days

- Parameningeal and paraspinal tumors allowed

- Patients with parameningeal (without intracranial extension [ICE]) and paraspinal
tumors should begin study chemotherapy at week 1 and radiotherapy at week 20

- Patients with evidence of ICE, as defined by contrast MRI showing that primary tumor
touches, displaces, invades, distorts, or otherwise causes a signal abnormality of the
dura in contiguity to the primary site in brain or spinal cord, are eligible

- ICE is presumed to exist if the cerebrospinal fluid cytopathology is positive for
tumor at diagnosis

- Patients requiring emergency radiotherapy are eligible

- Patients requiring emergency radiotherapy (for intracranial extension or spinal
cord impingement) should begin study chemotherapy at week 1 (irinotecan
hydrochloride and vincristine) concurrently with radiation therapy

PATIENT CHARACTERISTICS:

- ECOG or Zubrod performance status (PS) 0-2 (Lansky PS 50-100% for patients < 10 years
of age and Karnofsky PS 50-100% for patients = 10 years of age)

- Absolute neutrophil count = 750/mm³*

- Platelet count = 75,000/mm³*

- Creatinine clearance or radioisotope glomerular filtration rate = 70 mL/min (= 40
mL/min for infants < 1 year 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

- SGPT < 2.5 times normal

- Bilirubin < 1.5 mg/dL

- Shortening fraction = 27% by echocardiogram OR ejection fraction = 50% by MUGA

- Not pregnant or nursing

- Negative pregnancy test

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

- No evidence of uncontrolled infection

- Able to undergo radiotherapy NOTE: *Abnormal blood counts allowed if there is bone
marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy except steroids

- No prior radiotherapy

- No concurrent aprepitant during ifosfamide or doxorubicin hydrochloride chemotherapy

- No concurrent dexrazoxane

- No concurrent sargramostim (GM-CSF) or pegfilgrastim
Minimum age
No limit
Maximum age
49 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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 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
John Hunter Hospital - Newcastle
Recruitment hospital [2] 0 0
Westmead Institute for Cancer Research at Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Royal Children's Hospital - Herston, Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital - 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
2310 - Newcastle
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston, Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
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Arizona
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Arkansas
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Country [5] 0 0
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Country [6] 0 0
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Connecticut
Country [7] 0 0
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Delaware
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District of Columbia
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Massachusetts
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Michigan
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Mississippi
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Missouri
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Nebraska
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North Carolina
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Ohio
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Oklahoma
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Oregon
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Tennessee
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Utah
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Vermont
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West Virginia
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Alberta
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Switzerland
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Bern

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 vincristine, irinotecan, ifosfamide,
etoposide, doxorubicin, cyclophosphamide, and dactinomycin, work in different ways to stop
the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Radiation therapy uses high-energy x-rays to kill tumor cells. Giving high-dose combination
chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy
together with radiation therapy works in treating patients with newly diagnosed metastatic
rhabdomyosarcoma or ectomesenchymoma.
Trial website
https://clinicaltrials.gov/show/NCT00354744
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Brenda Weigel, MD
Address 0 0
Masonic Cancer Center, University of Minnesota
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