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| ID | Type | Description | Link |
|---|---|---|---|
| CDR0000612613 | Other Identifier | Clinical Trials.gov | |
| COG-AOST06P1 | Other Identifier | Children's Oncology Group |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
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.
OBJECTIVES:
Primary:
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1- Chemotherapy and 1.2 mg/m2 Zoledronic Acid | Experimental | (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. |
|
| Arm 2 - Chemotherapy and 2.3 mg/m2 Zoledronic Acid | Experimental | (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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cisplatin | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Limiting Toxicity | The occurrence of Limiting Toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:
| Enrollment through the first 12 weeks of therapy. |
| Measure | Description | Time Frame |
|---|---|---|
| Histologic Response as Assessed in the Primary Tumor and in Resected Metastases | Histologic response as graded according to the system of Huvos across all specimens resected at the time of local control in the primary tumor and in resected metastases. The best response, as quantified by maximum necrosis grading according to the system of Huvos across all specimens resected at the time of local control, will be used to quantify the effect of Induction chemotherapy. |
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DISEASE CHARACTERISTICS:
Biopsy-proven high-grade osteosarcoma within the past 6 weeks
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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Robert Goldsby, MD | University of California, San Francisco | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UAB Comprehensive Cancer Center | Birmingham | Alabama | 35294 | United States | ||
| Arkansas Cancer Research Center at University of Arkansas for Medical Sciences |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23664013 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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|
| Arm 3 - Chemotherapy and 3.5 mg/m2 Zoledronic Acid | Experimental | (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. |
|
| Chemotherapy and 2.3 mg/m2 Zoledronic Acid after MTD | Experimental | (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. |
|
|
| dexrazoxane hydrochloride | Drug | Given IV |
|
|
| doxorubicin hydrochloride | Drug | Given IV |
|
|
| etoposide | Drug | Given IV |
|
|
| ifosfamide | Drug | Given IV |
|
|
| leucovorin calcium | Drug | Given IV or orally |
|
|
| methotrexate | Drug | Given IV |
|
|
| zoledronic acid | Drug | Given IV |
|
|
| adjuvant therapy | Procedure |
|
| neoadjuvant therapy | Procedure |
|
| therapeutic conventional surgery | Procedure | Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy. |
|
| filgrastim | Biological | Given SC |
|
|
| Mesna | Drug | Given IV |
|
|
| At definitive surgery planned for 12 weeks after the start of protocol therapy. |
| Event-free Survival | The EFS and survival functions will be estimated by the Kaplan-Meier methodology. | Time from study enrollment to disease recurrence, death without disease progression, diagnosis of a second malignant neoplasm, assessed up to 5 years |
| Secondary Limiting Toxicity | Secondary limiting toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:
CTC AE version 4 hematologic toxicity will be based on time to blood count recovery to an ANC ≥ 1000/µL and platelet count ≥ 100,000/µL that delays definitive surgery by more than 2 weeks. | After week 13 to the end of protocol therapy |
| Prognostic Value of Bone Resorption Markers | Blood will be collected for quantification of c-telopeptide and urine will be collected for quantification of n-telopeptide. | At baseline and at weeks 13 and 36 |
| Little Rock |
| Arkansas |
| 72205 |
| United States |
| Southern California Permanente Medical Group | Downey | California | 90027 | United States |
| Jonathan Jaques Children's Cancer Center at Miller Children's Hospital | Long Beach | California | 90801 | United States |
| Childrens Hospital Los Angeles | Los Angeles | California | 90027 | United States |
| Children's Hospital Central California | Madera | California | 93638-8762 | United States |
| Children's Hospital and Research Center Oakland | Oakland | California | 94609 | United States |
| Children's Hospital of Orange County | Orange | California | 92868 | United States |
| Lucile Packard Children's Hospital Stanford University | Palo Alto | California | 94304 | United States |
| Rady Children's Hospital - San Diego | San Diego | California | 92123-4282 | United States |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | 94115 | United States |
| Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center | Farmington | Connecticut | 06360-2875 | United States |
| Alfred I. duPont Hospital for Children | Wilmington | Delaware | 19803 | United States |
| Children's National Medical Center | Washington D.C. | District of Columbia | 20010-2970 | United States |
| Nemours Children's Clinic | Jacksonville | Florida | 32207 | United States |
| Nemours Children's Clinic - Orlando | Orlando | Florida | 32806 | United States |
| Sacred Heart Cancer Center at Sacred Heart Hospital | Pensacola | Florida | 32504 | United States |
| All Children's Hospital | St. Petersburg | Florida | 33701 | United States |
| St. Joseph's Cancer Institute at St. Joseph's Hospital | Tampa | Florida | 33607 | United States |
| Kaplan Cancer Center at St. Mary's Medical Center | West Palm Beach | Florida | 33407 | United States |
| AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus | Atlanta | Georgia | 30322 | United States |
| Cancer Research Center of Hawaii | Honolulu | Hawaii | 96813 | United States |
| Mountain States Tumor Institute at St. Luke's Regional Medical Center | Boise | Idaho | 83712-6297 | United States |
| Children's Memorial Hospital - Chicago | Chicago | Illinois | 60614 | United States |
| Keyser Family Cancer Center at Advocate Hope Children's Hospital | Oak Lawn | Illinois | 60453 | United States |
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202-5289 | United States |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City | Iowa | 52242-1002 | United States |
| Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center | Kansas City | Kansas | 66160-7357 | United States |
| Lucille P. Markey Cancer Center at University of Kentucky | Lexington | Kentucky | 40536-0093 | United States |
| Kosair Children's Hospital | Louisville | Kentucky | 40232 | United States |
| Maine Children's Cancer Program at Barbara Bush Children's Hospital | Scarborough | Maine | 04074-9308 | United States |
| Alvin and Lois Lapidus Cancer Institute at Sinai Hospital | Baltimore | Maryland | 21215 | United States |
| Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| C.S. Mott Children's Hospital at University of Michigan Medical Center | Ann Arbor | Michigan | 48109-0286 | United States |
| Barbara Ann Karmanos Cancer Institute | Detroit | Michigan | 48201-1379 | United States |
| Butterworth Hospital at Spectrum Health | Grand Rapids | Michigan | 49503-2560 | United States |
| CCOP - Kalamazoo | Kalamazoo | Michigan | 49007-5381 | United States |
| Breslin Cancer Center at Ingham Regional Medical Center | Lansing | Michigan | 48910 | United States |
| Masonic Cancer Center at University of Minnesota | Minneapolis | Minnesota | 55455 | United States |
| Mayo Clinic Cancer Center | Rochester | Minnesota | 55905 | United States |
| University of Mississippi Cancer Clinic | Jackson | Mississippi | 39216-4505 | United States |
| Children's Mercy Hospital | Kansas City | Missouri | 64108 | United States |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St Louis | Missouri | 63110 | United States |
| Hackensack University Medical Center Cancer Center | Hackensack | New Jersey | 07601 | United States |
| Overlook Hospital | Morristown | New Jersey | 07962 | United States |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick | New Jersey | 08903 | United States |
| University of New Mexico Cancer Center | Albuquerque | New Mexico | 87131-5636 | United States |
| NYU Cancer Institute at New York University Medical Center | New York | New York | 10016 | United States |
| Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center | New York | New York | 10032 | United States |
| SUNY Upstate Medical University Hospital | Syracuse | New York | 13210 | United States |
| Blumenthal Cancer Center at Carolinas Medical Center | Charlotte | North Carolina | 28232-2861 | United States |
| Presbyterian Cancer Center at Presbyterian Hospital | Charlotte | North Carolina | 28233-3549 | United States |
| Duke Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem | North Carolina | 27157-1096 | United States |
| Akron Children's Hospital | Akron | Ohio | 44308-1062 | United States |
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229-3039 | United States |
| Rainbow Babies and Children's Hospital | Cleveland | Ohio | 44106-5000 | United States |
| Cleveland Clinic Taussig Cancer Center | Cleveland | Ohio | 44195 | United States |
| Nationwide Children's Hospital | Columbus | Ohio | 43205-2696 | United States |
| Dayton Children's - Dayton | Dayton | Ohio | 45404-1815 | United States |
| Oklahoma University Cancer Institute | Oklahoma City | Oklahoma | 73104 | United States |
| Knight Cancer Institute at Oregon Health and Science University | Portland | Oregon | 97239-3098 | United States |
| Penn State Children's Hospital | Hershey | Pennsylvania | 17033-0850 | United States |
| Palmetto Health South Carolina Cancer Center | Columbia | South Carolina | 29203 | United States |
| T.C. Thompson Children's Hospital | Chattanooga | Tennessee | 37403 | United States |
| East Tennessee Children's Hospital | Knoxville | Tennessee | 37901 | United States |
| Driscoll Children's Hospital | Corpus Christi | Texas | 78411 | United States |
| Medical City Dallas Hospital | Dallas | Texas | 75230 | United States |
| Cook Children's Medical Center - Fort Worth | Fort Worth | Texas | 76104 | United States |
| University of Texas Health Science Center at San Antonio | San Antonio | Texas | 78207 | United States |
| Methodist Children's Hospital of South Texas | San Antonio | Texas | 78229-3993 | United States |
| Primary Children's Medical Center | Salt Lake City | Utah | 84113-1100 | United States |
| Children's Hospital of The King's Daughters | Norfolk | Virginia | 23507-1971 | United States |
| Children's Hospital and Regional Medical Center - Seattle | Seattle | Washington | 98105 | United States |
| Providence Cancer Center at Sacred Heart Medical Center | Spokane | Washington | 99220-2555 | United States |
| West Virginia University Health Sciences Center - Charleston | Charleston | West Virginia | 25302 | United States |
| Marshfield Clinic - Marshfield Center | Marshfield | Wisconsin | 54449 | United States |
| Princess Margaret Hospital for Children | Perth | Western Australia | 6001 | Australia |
| Alberta Children's Hospital | Calgary | Alberta | T3B 6A8 | Canada |
| Children's & Women's Hospital of British Columbia | Vancouver | British Columbia | V6H 3V4 | Canada |
| CancerCare Manitoba | Winnipeg | Manitoba | R3E 0V9 | Canada |
| Janeway Children's Health and Rehabilitation Centre | St. John's | Newfoundland and Labrador | A1B 3V6 | Canada |
| IWK Health Centre | Halifax | Nova Scotia | B3K 6R8 | Canada |
| McMaster Children's Hospital at Hamilton Health Sciences | Hamilton | Ontario | L8N 3Z5 | Canada |
| Hospital for Sick Children | Toronto | Ontario | M5G 1X8 | Canada |
| Hopital Sainte Justine | Montreal | Quebec | H3T 1C5 | Canada |
| Saskatoon Cancer Centre at the University of Saskatchewan | Saskatoon | Saskatchewan | S7N 4H4 | Canada |
| San Jorge Children's Hospital | Santurce | 00912 | Puerto Rico |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Limiting Toxicity | The occurrence of Limiting Toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:
| Patients found not to meet the eligibility requirements are by group policy not followed for adverse events or outcome | Posted | Number | participants | Enrollment through the first 12 weeks of therapy. |
|
|
| |||||||||||||||||||||||||||||||||||
| Secondary | Histologic Response as Assessed in the Primary Tumor and in Resected Metastases | Histologic response as graded according to the system of Huvos across all specimens resected at the time of local control in the primary tumor and in resected metastases. The best response, as quantified by maximum necrosis grading according to the system of Huvos across all specimens resected at the time of local control, will be used to quantify the effect of Induction chemotherapy. | Not Posted | At definitive surgery planned for 12 weeks after the start of protocol therapy. | |||||||||||||||||||||||||||||||||||||||||
| Secondary | Event-free Survival | The EFS and survival functions will be estimated by the Kaplan-Meier methodology. | Not Posted | Time from study enrollment to disease recurrence, death without disease progression, diagnosis of a second malignant neoplasm, assessed up to 5 years | |||||||||||||||||||||||||||||||||||||||||
| Secondary | Secondary Limiting Toxicity | Secondary limiting toxicity defined as Any CTC AE version 4 Grade 3 and 4 non-hematologic toxicity thought to be possibly, probably or definitely related to zoledronic acid with the specific exclusion of:
CTC AE version 4 hematologic toxicity will be based on time to blood count recovery to an ANC ≥ 1000/µL and platelet count ≥ 100,000/µL that delays definitive surgery by more than 2 weeks. | Not Posted | After week 13 to the end of protocol therapy | |||||||||||||||||||||||||||||||||||||||||
| Secondary | Prognostic Value of Bone Resorption Markers | Blood will be collected for quantification of c-telopeptide and urine will be collected for quantification of n-telopeptide. | Not Posted | At baseline and at weeks 13 and 36 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 | 0 | 6 | 6 | 6 | ||
| EG001 | 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 | 0 | 6 | 6 | 6 | ||
| EG002 | 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 | 0 | 6 | 6 | 6 | ||
| EG003 | 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 | 0 | 6 | 5 | 6 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations |
| |||
| Anemia | Blood and lymphatic system disorders |
| |||
| Anorexia | Metabolism and nutrition disorders |
| |||
| Aspartate aminotransferase increased | Investigations |
| |||
| Dehydration | Metabolism and nutrition disorders |
| |||
| Edema limbs | General disorders |
| |||
| Enterocolitis infectious | Infections and infestations |
| |||
| Eye infection | Infections and infestations |
| |||
| Febrile neutropenia | Blood and lymphatic system disorders |
| |||
| Fracture | Injury, poisoning and procedural complications |
| |||
| Gingival pain | Gastrointestinal disorders |
| |||
| Hearing impaired | Ear and labyrinth disorders |
| |||
| Hyperglycemia | Metabolism and nutrition disorders |
| |||
| Hypermagnesemia | Metabolism and nutrition disorders |
| |||
| Hypocalcemia | Metabolism and nutrition disorders |
| |||
| Hypokalemia | Metabolism and nutrition disorders |
| |||
| Hyponatremia | Metabolism and nutrition disorders |
| |||
| Hypophosphatemia | Metabolism and nutrition disorders |
| |||
| Hypotension | Vascular disorders |
| |||
| Infections and infestations - Other, specify | Infections and infestations |
| |||
| Lymphocyte count decreased | Investigations |
| |||
| Mucositis oral | Gastrointestinal disorders |
| |||
| Nausea | Gastrointestinal disorders |
| |||
| Neutrophil count decreased | Investigations |
| |||
| Oral pain | Gastrointestinal disorders |
| |||
| Pain in extremity | Musculoskeletal and connective tissue disorders |
| |||
| Platelet count decreased | Investigations |
| |||
| Upper respiratory infection | Infections and infestations |
| |||
| Vomiting | Gastrointestinal disorders |
| |||
| White blood cell decreased | Investigations |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Results Reporting Coordinator | Children's Oncology Group | 352-273-0558 | resultsreportingcoordinator@childrensoncologygroup.org |
| ID | Term |
|---|---|
| D012509 | Sarcoma |
| D012516 | Osteosarcoma |
| ID | Term |
|---|---|
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D018213 | Neoplasms, Bone Tissue |
| D009372 | Neoplasms, Connective Tissue |
Not provided
Not provided
| ID | Term |
|---|---|
| D002945 | Cisplatin |
| D064730 | Dexrazoxane |
| D011929 | Razoxane |
| D004317 | Doxorubicin |
| D005047 | Etoposide |
| C061400 | etoposide phosphate |
| D007069 | Ifosfamide |
| D002955 | Leucovorin |
| D008727 | Methotrexate |
| D000077211 | Zoledronic Acid |
| D017024 | Chemotherapy, Adjuvant |
| D020360 | Neoadjuvant Therapy |
| D000069585 | Filgrastim |
| D016179 | Granulocyte Colony-Stimulating Factor |
| D015080 | Mesna |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D054659 | Diketopiperazines |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D005960 | Glucosides |
| D003520 | Cyclophosphamide |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D010078 | Oxazines |
| D005575 | Formyltetrahydrofolates |
| D013763 | Tetrahydrofolates |
| D005492 | Folic Acid |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D000630 | Aminopterin |
| D004164 | Diphosphonates |
| D063065 | Organophosphonates |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D003131 | Combined Modality Therapy |
| D013812 | Therapeutics |
| D004358 | Drug Therapy |
| D003115 | Colony-Stimulating Factors |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D016298 | Hematopoietic Cell Growth Factors |
| D016207 | Cytokines |
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D011506 | Proteins |
| D001685 | Biological Factors |
| D000476 | Alkanesulfonates |
| D017738 | Alkanesulfonic Acids |
| D000473 | Alkanes |
| D006839 | Hydrocarbons, Acyclic |
| D013438 | Sulfhydryl Compounds |
| D013457 | Sulfur Compounds |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Canada |
|