Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma
NCT ID: NCT00742924
Last Updated: 2014-07-04
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE1
24 participants
INTERVENTIONAL
2008-08-31
Brief Summary
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PURPOSE: This clinical trial is studying the side effects and best dose of zoledronic acid when given together with combination chemotherapy in treating patients with newly diagnosed metastatic osteosarcoma.
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Detailed Description
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Primary:
* To assess the feasibility and safety of zoledronic acid when administered in combination with standard chemotherapy in patients with newly diagnosed metastatic osteosarcoma.
* To determine the maximum tolerated dose of zoledronic acid when administered in combination with standard chemotherapy in these patients.
Secondary:
\- To compare the histologic response and event-free survival of patients treated with this regimen versus patients treated on INT-0133 or CCG-7943.
OUTLINE: This is a multicenter, dose-escalation study of zoledronic acid.
* Induction therapy (weeks 1-11): Patients receive dexrazoxane hydrochloride IV slowly over 5-15 minutes, doxorubicin hydrochloride IV over 15 minutes, and cisplatin IV over 1 hour on days 1 and 2 of weeks 1 and 6; zoledronic acid IV at the assigned dose level over 30 minutes on day 4 of weeks 1 and 6; high-dose methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and 10; leucovorin calcium IV or orally every 6 hours starting on day 2 and continuing until clearance of methotrexate of weeks 4, 5, 9, and 10; and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 of weeks 1 and 6 and continuing until blood counts recover.
* Surgery (week 12): Patients undergo definitive surgery (limb-salvage surgery or amputation) of the primary tumor in week 12.
* Maintenance therapy course 1 (weeks 13-25): Patients receive etoposide IV over 1 hour and ifosfamide IV over 4 hours on days 1-5 of weeks 13 and 21; zoledronic acid IV over 30 minutes on day 4 of week 17 and on day 7 of weeks 13 and 21; high-dose methotrexate IV over 4 hours on day 1 of weeks 16, 20, and 24; leucovorin calcium IV or orally every 6 hours starting on day 2 and continuing until clearance of methotrexate of weeks 16, 20, and 24; dexrazoxane hydrochloride IV slowly over 5-15 minutes, doxorubicin hydrochloride IV over 15 minutes, and cisplatin IV over 1 hour on days 1 and 2 of week 17; and G-CSF SC once daily beginning on day 6 of weeks 13, 17, and 21 and continuing until blood counts recover.
* Surgery (week 26): Patients may undergo surgical resection of primary metastases in week 26.
* Maintenance therapy course 2 (weeks 27-36): Patients receive dexrazoxane hydrochloride IV slowly over 5-15 minutes and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 of weeks 27 and 31; cisplatin IV over 1 hour on days 1 and 2 of week 27; zoledronic acid IV over 30 minutes on day 4 of week 27 and on day 7 of weeks 31 and 36; high-dose methotrexate IV over 4 hours on day 1 of weeks 30, 34, and 35; leucovorin calcium IV or orally every 6 hours starting on day 2 and continuing until clearance of methotrexate of weeks 30, 34, and 35; etoposide IV over 1 hour on days 1-5 of week 36; ifosfamide (1.8 gm/m2 ) IV over 1 hour on days 1-5 of week 31;ifosfamide (2.8 gm/m2)IV over 4 hours on days 1-5 of week 36; and G-CSF SC once daily beginning on day 3 of weeks 27, 31, and 36 and continuing until blood counts recover.
Mensa is a supportive care medicine used to prevent hemorrhagic cystitis caused by ifosfamide. It is always given when ifosfamide is given. It was used in all arms.
After completion of study treatment, patients are followed periodically for up to 5 years.
Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid
(Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery .
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
cisplatin
Given IV
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
etoposide
Given IV
ifosfamide
Given IV
leucovorin calcium
Given IV or orally
methotrexate
Given IV
zoledronic acid
Given IV
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
filgrastim
Given SC
Mesna
Given IV
Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid
(Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery.
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
cisplatin
Given IV
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
etoposide
Given IV
ifosfamide
Given IV
leucovorin calcium
Given IV or orally
methotrexate
Given IV
zoledronic acid
Given IV
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
filgrastim
Given SC
Mesna
Given IV
Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid
(Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery.
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
cisplatin
Given IV
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
etoposide
Given IV
ifosfamide
Given IV
leucovorin calcium
Given IV or orally
methotrexate
Given IV
zoledronic acid
Given IV
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
filgrastim
Given SC
Mesna
Given IV
Chemotherapy and 2.3 mg/m2 Zoledronic Acid after MTD
(Weeks 1-11) Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; and G-CSF SC. (Week 12) Patients undergo therapeutic conventional surgery.
(Weeks 13-25): Patients receive etoposide IV; ifosfamide IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; G-CSF SC. (Week 26) Patients may undergo surgical procedure.
(Weeks 27-36): Patients receive dexrazoxane hydrochloride IV; doxorubicin hydrochloride IV; cisplatin IV; zoledronic acid IV; high-dose methotrexate IV; leucovorin calcium IV or orally; etoposide IV; ifosfamide IV; and filgrastim (G-CSF) SC.
See Detailed Description.
cisplatin
Given IV
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
etoposide
Given IV
ifosfamide
Given IV
leucovorin calcium
Given IV or orally
methotrexate
Given IV
zoledronic acid
Given IV
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
filgrastim
Given SC
Mesna
Given IV
Interventions
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cisplatin
Given IV
dexrazoxane hydrochloride
Given IV
doxorubicin hydrochloride
Given IV
etoposide
Given IV
ifosfamide
Given IV
leucovorin calcium
Given IV or orally
methotrexate
Given IV
zoledronic acid
Given IV
adjuvant therapy
neoadjuvant therapy
therapeutic conventional surgery
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
filgrastim
Given SC
Mesna
Given IV
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Biopsy-proven high-grade osteosarcoma within the past 6 weeks
* Newly diagnosed disease
* Metastatic disease
* Resectable disease OR expected to become resectable after initial chemotherapy
* Disease has arisen outside of areas of Paget's disease
PATIENT CHARACTERISTICS:
* ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (for patients \> 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
* Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR maximum serum creatinine based on age/gender as follows:
* 0.4 mg/dL (for patients 1 to 5 months of age)
* 0.5 mg/dL (for patients 6 to 11 months of age)
* 0.6 mg/dL (for patients 1 year of age)
* 0.8 mg/dL (for patients 2 to 5 years of age)
* 1 mg/dL (for patients 6 to 9 years of age)
* 1.2 mg/dL (for patients 10 to 12 years of age)
* 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
* 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)
* Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age
* AST or ALT \< 2.5 times ULN for age
* Shortening fraction ≥ 28% by echocardiogram OR ejection fraction ≥ 50% by radionuclide angiogram
* ANC ≥ 1,000/mm³
* Platelet count ≥ 100,000/mm³ (transfusion independent)
* Hemoglobin ≥ 10 g/dL (RBC transfusion allowed)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use contraception
* No known HIV infection
* No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction disturbances
PRIOR CONCURRENT THERAPY:
* No prior chemotherapy or radiotherapy
* No other concurrent anticancer chemotherapy
* No concurrent immunomodulating agents
* Steroids for anti-emetic allowed
40 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Children's Oncology Group
NETWORK
Responsible Party
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Principal Investigators
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Robert Goldsby, MD
Role: STUDY_CHAIR
University of California, San Francisco
Locations
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UAB Comprehensive Cancer Center
Birmingham, Alabama, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Southern California Permanente Medical Group
Downey, California, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States
Children's Hospital Central California
Madera, California, United States
Children's Hospital and Research Center Oakland
Oakland, California, United States
Children's Hospital of Orange County
Orange, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
Rady Children's Hospital - San Diego
San Diego, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States
Children's National Medical Center
Washington D.C., District of Columbia, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
Nemours Children's Clinic - Orlando
Orlando, Florida, United States
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States
All Children's Hospital
St. Petersburg, Florida, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
Atlanta, Georgia, United States
Cancer Research Center of Hawaii
Honolulu, Hawaii, United States
Mountain States Tumor Institute at St. Luke's Regional Medical Center
Boise, Idaho, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Keyser Family Cancer Center at Advocate Hope Children's Hospital
Oak Lawn, Illinois, United States
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States
Kosair Children's Hospital
Louisville, Kentucky, United States
Maine Children's Cancer Program at Barbara Bush Children's Hospital
Scarborough, Maine, United States
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C.S. Mott Children's Hospital at University of Michigan Medical Center
Ann Arbor, Michigan, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Butterworth Hospital at Spectrum Health
Grand Rapids, Michigan, United States
CCOP - Kalamazoo
Kalamazoo, Michigan, United States
Breslin Cancer Center at Ingham Regional Medical Center
Lansing, Michigan, United States
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic Cancer Center
Rochester, Minnesota, United States
University of Mississippi Cancer Clinic
Jackson, Mississippi, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, United States
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States
Overlook Hospital
Morristown, New Jersey, United States
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
Albuquerque, New Mexico, United States
NYU Cancer Institute at New York University Medical Center
New York, New York, United States
Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
New York, New York, United States
SUNY Upstate Medical University Hospital
Syracuse, New York, United States
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States
Duke Comprehensive Cancer Center
Durham, North Carolina, United States
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States
Akron Children's Hospital
Akron, Ohio, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Dayton Children's - Dayton
Dayton, Ohio, United States
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States
Penn State Children's Hospital
Hershey, Pennsylvania, United States
Palmetto Health South Carolina Cancer Center
Columbia, South Carolina, United States
T.C. Thompson Children's Hospital
Chattanooga, Tennessee, United States
East Tennessee Children's Hospital
Knoxville, Tennessee, United States
Driscoll Children's Hospital
Corpus Christi, Texas, United States
Medical City Dallas Hospital
Dallas, Texas, United States
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States
Primary Children's Medical Center
Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, United States
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States
West Virginia University Health Sciences Center - Charleston
Charleston, West Virginia, United States
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States
Princess Margaret Hospital for Children
Perth, Western Australia, Australia
Alberta Children's Hospital
Calgary, Alberta, Canada
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Janeway Children's Health and Rehabilitation Centre
St. John's, Newfoundland and Labrador, Canada
IWK Health Centre
Halifax, Nova Scotia, Canada
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada
Hospital for Sick Children
Toronto, Ontario, Canada
Hopital Sainte Justine
Montreal, Quebec, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada
San Jorge Children's Hospital
Santurce, , Puerto Rico
Countries
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References
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Goldsby RE, Fan TM, Villaluna D, Wagner LM, Isakoff MS, Meyer J, Randall RL, Lee S, Kim G, Bernstein M, Gorlick R, Krailo M, Marina N. Feasibility and dose discovery analysis of zoledronic acid with concurrent chemotherapy in the treatment of newly diagnosed metastatic osteosarcoma: a report from the Children's Oncology Group. Eur J Cancer. 2013 Jul;49(10):2384-91. doi: 10.1016/j.ejca.2013.03.018. Epub 2013 May 7.
Other Identifiers
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CDR0000612613
Identifier Type: OTHER
Identifier Source: secondary_id
COG-AOST06P1
Identifier Type: OTHER
Identifier Source: secondary_id
AOST06P1
Identifier Type: -
Identifier Source: org_study_id
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