Cardiac ToxicityPhase 3NCT00003937
Combination Chemotherapy Plus Dexrazoxane in Treating Patients With Newly Diagnosed Nonmetastatic Osteosarcoma
A Phase 3 study testing cisplatin, dexrazoxane hydrochloride and doxorubicin hydrochloride in people with Cardiac Toxicity and Sarcoma, run by Children's Oncology Group at 148 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Cardiac Toxicity, Sarcoma
- What is being tested?
- cisplatin, dexrazoxane hydrochloride and doxorubicin hydrochloride
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 253 participants
- Where
- 148 sitesin 6 countries
- Study dates
- Sep 1999to Jun 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
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
Trial locations and contacts
148 sites in 6 countries.
148 sites in 6 countries
United States132 sites
University of New Mexico School of Medicine
Albuquerque, New Mexico, 87131
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0752
Mission Saint Joseph's Health System
Asheville, North Carolina, 28801
Emory University Hospital - Atlanta
Atlanta, Georgia, 30322
Marlene & Stewart Greenebaum Cancer Center, University of Maryland
Baltimore, Maryland, 21201
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
Eastern Maine Medical Center
Bangor, Maine, 04401
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, 35294-3300
Boston Floating Hospital Infants and Children
Boston, Massachusetts, 02111
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Roswell Park Cancer Institute
Buffalo, New York, 14263-0001
Vermont Cancer Center
Burlington, Vermont, 05401-3498
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, 27599-7295
Medical University of South Carolina
Charleston, South Carolina, 29425-0721
West Virginia University Medical School-Charleston
Charleston, West Virginia, 25304
Carolinas Medical Center
Charlotte, North Carolina, 28232-2861
Presbyterian Healthcare
Charlotte, North Carolina, 28233-3549
Cancer Center at the University of Virginia
Charlottesville, Virginia, 22908
Rush-Presbyterian-St. Luke's Medical Center
Chicago, Illinois, 60612
Children's Memorial Hospital, Chicago
Chicago, Illinois, 60614
University of Chicago Cancer Research Center
Chicago, Illinois, 60637-1470
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, 45229-3039
Ireland Cancer Center
Cleveland, Ohio, 44106-5065
University of Missouri-Columbia Hospital and Clinics
Columbia, Missouri, 65212
Children's Hospital of Columbus
Columbus, Ohio, 43205-2696
Texas Oncology P.A.
Dallas, Texas, 75230-2503
Medical City Dallas Hospital
Dallas, Texas, 75230
Simmons Cancer Center - Dallas
Dallas, Texas, 75235-9154
Children's Hospital of Denver
Denver, Colorado, 80218
Children's Hospital of Michigan
Detroit, Michigan, 48201
St. John's Hospital and Medical Center
Detroit, Michigan, 48236
Duke Comprehensive Cancer Center
Durham, North Carolina, 27710
Inova Fairfax Hospital
Falls Church, Virginia, 22042-3300
Veterans Affairs Medical Center - Fargo
Fargo, North Dakota, 58102
CCOP - Merit Care Hospital
Fargo, North Dakota, 58122
Hurley Medical Center
Flint, Michigan, 48503
Shands Hospital and Clinics, University of Florida
Gainesville, Florida, 32610-100277
University of Texas Medical Branch
Galveston, Texas, 77555-0209
St. Vincent Hospital
Green Bay, Wisconsin, 54307-3508
East Carolina University School of Medicine
Greenville, North Carolina, 27858-4354
Children's Hospital of Greenville Hospital System
Greenville, South Carolina, 29605
CCOP - Northern New Jersey
Hackensack, New Jersey, 07601
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cancer Research Center of Hawaii
Honolulu, Hawaii, 96813
Tripler Army Medical Center
Honolulu, Hawaii, 96859-5000
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030-4009
Baylor College of Medicine
Houston, Texas, 77030
Indiana University Cancer Center
Indianapolis, Indiana, 46202-5289
Holden Comprehensive Cancer Center at The University of Iowa
Iowa City, Iowa, 52242-1009
University of Mississippi Medical Center
Jackson, Mississippi, 39216-4505
Nemours Children's Clinic
Jacksonville, Florida, 32207
James H. Quillen College of Medicine
Johnson City, Tennessee, 37614-0622
CCOP - Kalamazoo
Kalamazoo, Michigan, 49007-3731
University of Kansas Medical Center
Kansas City, Kansas, 66160-7357
Children's Mercy Hospital
Kansas City, Missouri, 64108
Keesler Medical Center - Keesler AFB
Keesler Air Force Base, Mississippi, 39534-2576
University of California San Diego Cancer Center
La Jolla, California, 92093-0658
San Antonio Military Pediatric Cancer and Blood Disorders Center
Lackland Air Force Base, Texas, 78236-5300
Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756-0002
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Long Beach Memorial Medical Center
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, 90095-1781
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, 53792-6164
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794
Sylvester Cancer Center, University of Miami
Miami, Florida, 33136
Miami Children's Hospital
Miami, Florida, 33155
Baptist Hospital of Miami
Miami, Florida, 33176-2197
Midwest Children's Cancer Center
Milwaukee, Wisconsin, 53226
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
MBCCOP - Gulf Coast
Mobile, Alabama, 36688
West Virginia University Hospitals
Morgantown, West Virginia, 26506-9300
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
Cancer Institute of New Jersey
New Brunswick, New Jersey, 08901
Yale Comprehensive Cancer Center
New Haven, Connecticut, 06520-8028
Schneider Children's Hospital
New Hyde Park, New York, 11042
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, 70112
Tulane University School of Medicine
New Orleans, Louisiana, 70112
CCOP - Ochsner
New Orleans, Louisiana, 70121
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Mount Sinai School of Medicine
New York, New York, 10029
Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Hope Children's Hospital
Oak Lawn, Illinois, 60453
Oklahoma Memorial Hospital
Oklahoma City, Oklahoma, 73126-0307
University of Nebraska Medical Center
Omaha, Nebraska, 68198-3330
Children's Hospital of Orange County
Orange, California, 92868
Walt Disney Memorial Cancer Institute
Orlando, Florida, 32803
Lucile Packard Children's Hospital at Stanford
Palo Alto, California, 94304
CCOP - Illinois Oncology Research Association
Peoria, Illinois, 61602
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134-1095
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Maine Children's Cancer Program
Portland, Maine, 04101
Doernbecher Children's Hospital
Portland, Oregon, 97201-3098
CCOP - Columbia River Program
Portland, Oregon, 97213
Legacy Emanuel Hospital and Health Center
Portland, Oregon, 97227
Naval Medical Center, Portsmouth
Portsmouth, Virginia, 23708-2197
Massey Cancer Center
Richmond, Virginia, 23298-0037
Carilion Roanoke Community Hospital
Roanoke, Virginia, 24029
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
University of Rochester Cancer Center
Rochester, New York, 14642
Sutter Cancer Center
Sacramento, California, 95816
University of California Davis Medical Center
Sacramento, California, 95817
MBCCOP - South Texas Pediatric
San Antonio, Texas, 78229-3900
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78284-7811
Kaiser Permanente-Southern California Permanente Medical Group
San Diego, California, 92120
Children's Hospital and Health Center
San Diego, California, 92123-4282
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, 94143-0128
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, 95051-5386
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024
Cardinal Glennon Children's Hospital
St Louis, Missouri, 63104
Washington University School of Medicine
St Louis, Missouri, 63110
All Children's Hospital
St. Petersburg, Florida, 33701
State University of New York Health Sciences Center - Stony Brook
Stony Brook, New York, 11790-7775
State University of New York - Upstate Medical University
Syracuse, New York, 13210
Madigan Army Medical Center
Tacoma, Washington, 98431-5000
CCOP - Florida Pediatric
Tampa, Florida, 33682-7757
Scott and White Clinic
Temple, Texas, 76508
David Grant Medical Center
Travis Air Force Base, California, 94535
Arizona Cancer Center
Tucson, Arizona, 85724
Natalie Warren Bryant Cancer Center
Tulsa, Oklahoma, 74136
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
Walter Reed Army Medical Center
Washington D.C., District of Columbia, 20307-5000
St. Mary's Hospital
West Palm Beach, Florida, 33407
CCOP - Wichita
Wichita, Kansas, 67214-3882
Via Christi Regional Medical Center
Wichita, Kansas, 67214
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, 27157-1082
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655
Canada10 sites
Alberta Children's Hospital
Calgary, Alberta, T2T 5C7
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
IWK Health Centre
Halifax, Nova Scotia, B3J 3G9
Children's Hospital
Hamilton, Ontario, L8N 3Z5
McGill University Health Center - Montreal Children's Hospital
Montreal, Quebec, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Centre Hospitalier de L'Universite Laval
Sainte-Foy, Quebec, GIV 4G2
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
Australia2 sites
Royal Children's Hospital
Parkville, Victoria, 3052
Princess Margaret Hospital for Children
Perth, Western Australia, 6001
Switzerland2 sites
Swiss Pediatric Oncology Group Bern
Bern, CH 3010
Clinique de Pediatrie
Geneva, 1211
About this study
Official title: Protocol for Patients With Newly-Diagnosed Non-Metastatic Osteosarcoma - A POG/CCG Pilot Intergroup Study
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.
Read the detailed 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.
- Conditions
- Cardiac Toxicity, Sarcoma
- Being tested
- cisplatin, dexrazoxane hydrochloride, doxorubicin hydrochloride, etoposide, ifosfamide
- Keywords
- localized osteosarcoma, cardiac toxicity
- Medical subject headings
- Cardiotoxicity, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cisplatinDrug
Also called Cis-diamminedichloroplatinum II, CDDP, Platinol, NSC #119875
dexrazoxane hydrochlorideDrug
Also called ADR-529, ZINECARD, ICRF-187, NSC #169780
Also called Adriamycin, NSC #123127
etoposideDrug
Also called VP-16, VePesid, NSC #141540
ifosfamideDrug
Also called IFX, IFOS, NSC #109724
methotrexateDrug
Also called MTX, amethopterin, NSC #000740
conventional surgeryProcedure or surgery
| Study group | Role | What they receive |
|---|---|---|
| Pilot 1 - Doxorubicin Intensification without Ifosfamide | Experimental | 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. Receives: Drug: cisplatin; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: methotrexate; Procedure: conventional surgery |
| Pilot 2 - Doxorubicin Intensification with Ifosfamide | Experimental | 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 Receives: Drug: cisplatin; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: ifosfamide; Drug: methotrexate; Procedure: conventional surgery |
| Pilot 3 - Ifosfamide/Etoposide Intensification | Experimental | 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 Receives: Drug: cisplatin; Drug: dexrazoxane hydrochloride; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: methotrexate; Procedure: conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2004 (estimated)
- Study startSep 1999
- Primary completionMar 2004
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cardiac ToxicityStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 253 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Cindy Schwartz, MD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003937
- Sponsor's protocol ID
- P9754
- Other IDs
- COG-P9754, POG-P9754, CCG-P9754, CDR0000067129
- Status last verified
- Aug 2014
- First submitted
- 1 Nov 1999
- Last updated
- 5 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 22354612Janeway 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.
PubMed 22252521Kopp 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.
PubMed 32154021
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol for Patients With Newly-Diagnosed Non-Metastatic Osteosarcoma - A POG/CCG Pilot Intergroup Study
- ClinicalTrials.gov ID
- NCT00003937
- Acronym / sponsor ID
- P9754
- Conditions
- Cardiac Toxicity, Sarcoma
- Keywords
- localized osteosarcoma, cardiac toxicity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 253 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 1999
- Primary completion
- Mar 2004 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 9 Feb 2004 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pilot 1 - Doxorubicin Intensification without Ifosfamide | Experimental | Drug: cisplatin, Drug: dexrazoxane hydrochloride, Drug: doxorubicin hydrochloride, Drug: methotrexate, Procedure: conventional surgeryDexrazoxane 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. |
| Pilot 2 - Doxorubicin Intensification with Ifosfamide | Experimental | Drug: cisplatin, Drug: dexrazoxane hydrochloride, Drug: doxorubicin hydrochloride, Drug: ifosfamide, Drug: methotrexate, Procedure: conventional surgeryPreoperative 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 |
| Pilot 3 - Ifosfamide/Etoposide Intensification | Experimental | Drug: cisplatin, Drug: dexrazoxane hydrochloride, Drug: doxorubicin hydrochloride, Drug: etoposide, Drug: ifosfamide, Drug: methotrexate, Procedure: conventional surgeryPreoperative 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 |
Who may qualify
- Ages
- Up to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cisplatinAlso: Cis-diamminedichloroplatinum II, CDDP, Platinol, NSC #119875 | Drug | Pilot 1 - Doxorubicin Intensification without Ifosfamide, Pilot 2 - Doxorubicin Intensification with Ifosfamide, Pilot 3 - Ifosfamide/Etoposide Intensification |
| dexrazoxane hydrochlorideAlso: ADR-529, ZINECARD, ICRF-187, NSC #169780 | Drug | Pilot 1 - Doxorubicin Intensification without Ifosfamide, Pilot 2 - Doxorubicin Intensification with Ifosfamide, Pilot 3 - Ifosfamide/Etoposide Intensification |
| doxorubicin hydrochlorideAlso: Adriamycin, NSC #123127 | Drug | Pilot 1 - Doxorubicin Intensification without Ifosfamide, Pilot 2 - Doxorubicin Intensification with Ifosfamide, Pilot 3 - Ifosfamide/Etoposide Intensification |
| etoposideAlso: VP-16, VePesid, NSC #141540 | Drug | Pilot 3 - Ifosfamide/Etoposide Intensification |
| ifosfamideAlso: IFX, IFOS, NSC #109724 | Drug | Pilot 2 - Doxorubicin Intensification with Ifosfamide, Pilot 3 - Ifosfamide/Etoposide Intensification |
| methotrexateAlso: MTX, amethopterin, NSC #000740 | Drug | Pilot 1 - Doxorubicin Intensification without Ifosfamide, Pilot 2 - Doxorubicin Intensification with Ifosfamide, Pilot 3 - Ifosfamide/Etoposide Intensification |
| conventional surgery | Procedure or surgery | Pilot 1 - Doxorubicin Intensification without Ifosfamide, Pilot 2 - Doxorubicin Intensification with Ifosfamide, Pilot 3 - Ifosfamide/Etoposide Intensification |
Primary outcome
Event Free Survival
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Aug 2014.
- Background: PubMed 22354612Isakoff 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.
- Background: PubMed 22252521Janeway 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.
- Derived from this study: PubMed 32154021Kopp 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Cindy Schwartz, MD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
148 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing cisplatin, dexrazoxane hydrochloride and doxorubicin hydrochloride in people with Cardiac Toxicity and Sarcoma, run by Children's Oncology Group at 148 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 148 sites in United States, Canada, Australia, Switzerland, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event Free Survival. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00003937, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2014.