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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00003937




Registration number
NCT00003937
Ethics application status
Date submitted
1/11/1999
Date registered
9/02/2004
Date last updated
5/08/2014

Titles & IDs
Public title
Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma
Scientific title
Protocol for Patients With Newly-Diagnosed Non-Metastatic Osteosarcoma - A POG/CCG Pilot Intergroup Study
Secondary ID [1] 0 0
COG-P9754
Secondary ID [2] 0 0
P9754
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Toxicity 0 0
Sarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Children's - Other
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Experimental: Pilot 1 - Doxorubicin Intensification without Ifosfamide - Dexrazoxane hydrochloride IV followed by doxorubicin hydrochloride IV plus cisplatin IV on days 1 and 2 of weeks 1 and 6. Methotrexate IV on day 1 of weeks 4, 5, 9, and 10. Patients undergo surgery on week 11. Adjuvant chemotherapy begins on day 1 of week 13. Group 1 (good response to neoadjuvant chemotherapy): Patients receive methotrexate IV over 4 hours every 3 weeks for 6 courses, beginning on week 13. Patients also receive dexrazoxane and doxorubicin hydrochloride every 3 weeks for 4 courses, beginning on week 14. Cisplatin is administered with the first 2 courses of dexrazoxane and doxorubicin. Group 2 (standard response to neoadjuvant chemotherapy): Patients receive methotrexate and cisplatin as in group 1 plus dexrazoxane and doxorubicin hydrochloride for 6 courses.

Experimental: Pilot 2 - Doxorubicin Intensification with Ifosfamide - Preoperative therapy comprised of dexrazoxane hydrochloride, doxorubicin hydrochloride, and methotrexate as in pilot 1. Ifosfamide IV on days 1-5 of week 1. Patients undergo surgery on week 11, then begin adjuvant chemotherapy on week 13. Group 1: Patients receive methotrexate, dexrazoxane hydrochloride, and doxorubicin hydrochloride as in pilot 1, group 1. Ifosfamide is also administered on weeks 14 and 20. Cisplatin is administered on weeks 17, 23, and 26. Group 2: Patients receive methotrexate, dexrazoxane hydrochloride, and doxorubicin hydrochloride as in pilot 1, group 2. Ifosfamide is administered on weeks 14, 20, 26, and 31. Cisplatin is administered on weeks 17, 23, and 29

Experimental: Pilot 3 - Ifosfamide/Etoposide Intensification - Preoperative therapy comprised of methotrexate, dexrazoxane hydrochloride, doxorubicin, ifosfamide, and cisplatin as in pilot 2. Patients undergo surgery on week 11, then begin adjuvant chemotherapy on week 13. Group 1: Patients receive methotrexate, dexrazoxane hydrochloride, doxorubicin, ifosfamide, and cisplatin as in pilot 2, group 1. Group 2: Patients receive methotrexate on weeks 13, 19, 29, 32, 35, and 36, high dose ifosfamide and etoposide IV over 4 hours on days 1-5 of weeks 14, 23, and 26, and cisplatin on weeks 20, 30, and 33. Dexrazoxane hydrochloride and doxorubicin hydrochloride are administered on weeks 17, 20, 30, and 33
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Event Free Survival
Timepoint [1] 0 0

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS: Histologically proven newly diagnosed moderate or high grade osteosarcoma without metastases No prior treatment, including complete resection No parosteal or periosteal sarcoma No osteosarcoma associated with Paget's disease No nonresectable tumors or tumors that may result in marginal or interlesion resection Must be enrolled on protocol POG-9851

PATIENT CHARACTERISTICS: Age: 30 and under Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 1.5 times normal SGOT no greater than 3 times normal Renal: Creatinine normal Phosphate at least 3.0 mg/dL without supplementation Cardiovascular: Shortening fraction at least 28% by echocardiogram If echocardiogram unsatisfactory, must have ejection fraction at least 50% No history of pericarditis or myocarditis No symptomatic arrhythmia or symptomatic cardiac conduction disturbances

PRIOR CONCURRENT THERAPY: See Disease Characteristics Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy Surgery: See Disease Characteristics
Minimum age
No limit
Maximum age
30 Years
Sex
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
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
1/09/1999
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2008
Sample size
Target
Accrual to date
Final
253
Recruitment in Australia
Recruitment state(s)
VIC,WA
Recruitment hospital [1] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [2] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
3052 - Parkville
Recruitment postcode(s) [2] 0 0
6001 - 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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Colorado
Country [6] 0 0
United States of America
State/province [6] 0 0
Connecticut
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Hawaii
Country [11] 0 0
United States of America
State/province [11] 0 0
Illinois
Country [12] 0 0
United States of America
State/province [12] 0 0
Indiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Iowa
Country [14] 0 0
United States of America
State/province [14] 0 0
Kansas
Country [15] 0 0
United States of America
State/province [15] 0 0
Louisiana
Country [16] 0 0
United States of America
State/province [16] 0 0
Maine
Country [17] 0 0
United States of America
State/province [17] 0 0
Maryland
Country [18] 0 0
United States of America
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Massachusetts
Country [19] 0 0
United States of America
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Michigan
Country [20] 0 0
United States of America
State/province [20] 0 0
Minnesota
Country [21] 0 0
United States of America
State/province [21] 0 0
Mississippi
Country [22] 0 0
United States of America
State/province [22] 0 0
Missouri
Country [23] 0 0
United States of America
State/province [23] 0 0
Nebraska
Country [24] 0 0
United States of America
State/province [24] 0 0
New Hampshire
Country [25] 0 0
United States of America
State/province [25] 0 0
New Jersey
Country [26] 0 0
United States of America
State/province [26] 0 0
New Mexico
Country [27] 0 0
United States of America
State/province [27] 0 0
New York
Country [28] 0 0
United States of America
State/province [28] 0 0
North Carolina
Country [29] 0 0
United States of America
State/province [29] 0 0
North Dakota
Country [30] 0 0
United States of America
State/province [30] 0 0
Ohio
Country [31] 0 0
United States of America
State/province [31] 0 0
Oklahoma
Country [32] 0 0
United States of America
State/province [32] 0 0
Oregon
Country [33] 0 0
United States of America
State/province [33] 0 0
Pennsylvania
Country [34] 0 0
United States of America
State/province [34] 0 0
South Carolina
Country [35] 0 0
United States of America
State/province [35] 0 0
Tennessee
Country [36] 0 0
United States of America
State/province [36] 0 0
Texas
Country [37] 0 0
United States of America
State/province [37] 0 0
Vermont
Country [38] 0 0
United States of America
State/province [38] 0 0
Virginia
Country [39] 0 0
United States of America
State/province [39] 0 0
Washington
Country [40] 0 0
United States of America
State/province [40] 0 0
West Virginia
Country [41] 0 0
United States of America
State/province [41] 0 0
Wisconsin
Country [42] 0 0
Canada
State/province [42] 0 0
Alberta
Country [43] 0 0
Canada
State/province [43] 0 0
British Columbia
Country [44] 0 0
Canada
State/province [44] 0 0
Nova Scotia
Country [45] 0 0
Canada
State/province [45] 0 0
Ontario
Country [46] 0 0
Canada
State/province [46] 0 0
Quebec
Country [47] 0 0
Netherlands
State/province [47] 0 0
Groningen
Country [48] 0 0
Puerto Rico
State/province [48] 0 0
Santurce
Country [49] 0 0
Switzerland
State/province [49] 0 0
Bern
Country [50] 0 0
Switzerland
State/province [50] 0 0
Geneva

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 use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Chemoprotective drugs such as dexrazoxane may protect normal cells from the side effects of chemotherapy.

PURPOSE: Phase III trial to study the effectiveness of three combination chemotherapy regimens plus dexrazoxane in treating patients who have newly diagnosed nonmetastatic osteosarcoma.
Trial website
https://clinicaltrials.gov/study/NCT00003937
Trial related presentations / publications
Isakoff MS, Barkauskas DA, Ebb D, Morris C, Letson GD. Poor survival for osteosarcoma of the pelvis: a report from the Children's Oncology Group. Clin Orthop Relat Res. 2012 Jul;470(7):2007-13. doi: 10.1007/s11999-012-2284-9. Epub 2012 Feb 22.
Janeway KA, Barkauskas DA, Krailo MD, Meyers PA, Schwartz CL, Ebb DH, Seibel NL, Grier HE, Gorlick R, Marina N. Outcome for adolescent and young adult patients with osteosarcoma: a report from the Children's Oncology Group. Cancer. 2012 Sep 15;118(18):4597-605. doi: 10.1002/cncr.27414. Epub 2012 Jan 17.
Kopp LM, Womer RB, Schwartz CL, Ebb DH, Franco VI, Hall D, Barkauskas DA, Krailo MD, Grier HE, Meyers PA, Wexler LH, Marina NM, Janeway KA, Gorlick R, Bernstein ML, Lipshultz SE; Children's Oncology Group. Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children's Oncology Group. Cardiooncology. 2019 Oct 28;5:15. doi: 10.1186/s40959-019-0050-9. eCollection 2019.
Public notes

Contacts
Principal investigator
Name 0 0
Cindy Schwartz, MD
Address 0 0
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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/study/NCT00003937