Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma

Sarcoma Clinical Trial

Official title:

Protocol for Patients With Newly-Diagnosed Non-Metastatic Osteosarcoma - A POG/CCG Pilot Intergroup Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003937
• Other study ID #: P9754
• Secondary ID: COG-P9754POG-P97
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: August 4, 2014
• Start date: September 1999
• Est. completion date: June 2008

Study information

• Verified date: August 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

Description:

OBJECTIVES: I. Compare the efficacy of three intensification regimens (doxorubicin vs doxorubicin plus ifosfamide vs doxorubicin plus ifosfamide and etoposide) in patients with newly diagnosed, previously untreated, nonmetastatic osteosarcoma. II. Determine the effect of postoperative dose intensification on outcome in patients with standard response to preoperative chemotherapy. III. Determine the effect of dexrazoxane cardioprotection during standard induction therapy on histologic response in these patients. IV. Evaluate biological factors that may predict outcome in these patients. V. Determine the safety of dexrazoxane administered with doxorubicin in combination with cisplatin or cisplatin and ifosfamide in these patients. VI. Determine the effect of dexrazoxane on cytotoxicity as measured by tumor necrosis at definitive surgery in these patients. VII. Assess the feasibility of administering doxorubicin with dexrazoxane cardioprotection or high dose ifosfamide with etoposide to standard risk patients who are also receiving methotrexate and cisplatin.

OUTLINE: This is a multicenter study. Patients are enrolled sequentially on 1 of 3 pilot intensification regimens. After surgery to completely remove the primary tumor, patients are assigned to 1 of 2 adjuvant chemotherapy groups based on percent necrosis at limb salvage. Pilot 1: (Closed to accrual as of 6/2/2000) Patients receive dexrazoxane IV followed immediately by doxorubicin IV over 20 minutes plus cisplatin IV over 4 hours on days 1 and 2 of weeks 1 and 6. Methotrexate IV over 4 hours is administered 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 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 for 6 courses. Pilot 2: Patients receive preoperative therapy comprised of dexrazoxane, doxorubicin, and methotrexate as in pilot 1. Ifosfamide IV over 4 hours is also administered 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, and doxorubicin 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, and doxorubicin 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. Pilot 3: (Open to accrual as of 6/2/2000) Patients receive preoperative therapy comprised of methotrexate, dexrazoxane, 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, 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 and doxorubicin are administered on weeks 17, 20, 30, and 33. Patients are followed every 3 months for 1 year, every 6 months for 4 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 180 patients will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 253
• Est. completion date: June 2008
• Est. primary completion date: March 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 30 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Toxicity
• Osteosarcoma
• Sarcoma

Intervention

Drug:
• cisplatin

• dexrazoxane hydrochloride

• doxorubicin hydrochloride

• etoposide

• ifosfamide

• methotrexate

Procedure:
• conventional surgery

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Children's Hospital	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec
Canada	Children's Hospital of Eastern Ontario	Ottawa	Ontario
Canada	Centre Hospitalier de L'Universite Laval	Sainte Foy	Quebec
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Netherlands	Academisch Ziekenhuis Groningen	Groningen
Puerto Rico	San Jorge Childrens Hospital	Santurce
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Clinique de Pediatrie	Geneva
United States	University of New Mexico School of Medicine	Albuquerque	New Mexico
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Mission Saint Joseph's Health System	Asheville	North Carolina
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Marlene & Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama at Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Boston Floating Hospital Infants and Children	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Vermont Cancer Center	Burlington	Vermont
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Medical School-Charleston	Charleston	West Virginia
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	Presbyterian Healthcare	Charlotte	North Carolina
United States	Cancer Center at the University of Virginia	Charlottesville	Virginia
United States	Children's Memorial Hospital, Chicago	Chicago	Illinois
United States	Rush-Presbyterian-St. Luke's Medical Center	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Children's Hospital Medical Center - Cincinnati	Cincinnati	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	University of Missouri-Columbia Hospital and Clinics	Columbia	Missouri
United States	Children's Hospital of Columbus	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	Simmons Cancer Center - Dallas	Dallas	Texas
United States	Texas Oncology P.A.	Dallas	Texas
United States	Children's Hospital of Denver	Denver	Colorado
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	St. John's Hospital and Medical Center	Detroit	Michigan
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Veterans Affairs Medical Center - Fargo	Fargo	North Dakota
United States	Hurley Medical Center	Flint	Michigan
United States	Shands Hospital and Clinics, University of Florida	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Children's Hospital of Greenville Hospital System	Greenville	South Carolina
United States	East Carolina University School of Medicine	Greenville	North Carolina
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Tripler Army Medical Center	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas - MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	James H. Quillen College of Medicine	Johnson City	Tennessee
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Keesler Medical Center - Keesler AFB	Keesler AFB	Mississippi
United States	University of California San Diego Cancer Center	La Jolla	California
United States	San Antonio Military Pediatric Cancer and Blood Disorders Center	Lackland Air Force Base	Texas
United States	Norris Cotton Cancer Center	Lebanon	New Hampshire
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Saint Jude Children's Research Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Miami Children's Hospital	Miami	Florida
United States	Sylvester Cancer Center, University of Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	MBCCOP - Gulf Coast	Mobile	Alabama
United States	West Virginia University Hospitals	Morgantown	West Virginia
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Yale Comprehensive Cancer Center	New Haven	Connecticut
United States	Schneider Children's Hospital	New Hyde Park	New York
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Tulane University School of Medicine	New Orleans	Louisiana
United States	Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Hope Children's Hospital	Oak Lawn	Illinois
United States	Oklahoma Memorial Hospital	Oklahoma City	Oklahoma
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Orange County	Orange	California
United States	Walt Disney Memorial Cancer Institute	Orlando	Florida
United States	Lucile Packard Children's Hospital at Stanford	Palo Alto	California
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	CCOP - Columbia River Program	Portland	Oregon
United States	Doernbecher Children's Hospital	Portland	Oregon
United States	Legacy Emanuel Hospital and Health Center	Portland	Oregon
United States	Maine Children's Cancer Program	Portland	Maine
United States	Naval Medical Center, Portsmouth	Portsmouth	Virginia
United States	Massey Cancer Center	Richmond	Virginia
United States	Carilion Roanoke Community Hospital	Roanoke	Virginia
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of Rochester Cancer Center	Rochester	New York
United States	Sutter Cancer Center	Sacramento	California
United States	University of California Davis Medical Center	Sacramento	California
United States	Cardinal Glennon Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	MBCCOP - South Texas Pediatric	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Children's Hospital and Health Center	San Diego	California
United States	Kaiser Permanente-Southern California Permanente Medical Group	San Diego	California
United States	UCSF Cancer Center and Cancer Research Institute	San Francisco	California
United States	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	All Children's Hospital	St. Petersburg	Florida
United States	State University of New York Health Sciences Center - Stony Brook	Stony Brook	New York
United States	State University of New York - Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	CCOP - Florida Pediatric	Tampa	Florida
United States	Scott and White Clinic	Temple	Texas
United States	David Grant Medical Center	Travis Air Force Base	California
United States	Arizona Cancer Center	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center	Tulsa	Oklahoma
United States	Children's National Medical Center	Washington	District of Columbia
United States	Walter Reed Army Medical Center	Washington	District of Columbia
United States	St. Mary's Hospital	West Palm Beach	Florida
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Regional Medical Center	Wichita	Kansas
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Netherlands,  Puerto Rico,  Switzerland, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Free Survival			No