Know Cancer

or
forgot password

A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-Operative Chemotherapy (IND# 12697)


Phase 3
5 Years
40 Years
Open (Enrolling)
Both
Localized Osteosarcoma, Metastatic Osteosarcoma

Thank you

Trial Information

A Randomized Trial of the European and American Osteosarcoma Study Group to Optimize Treatment Strategies for Resectable Osteosarcoma Based on Histological Response to Pre-Operative Chemotherapy (IND# 12697)


PRIMARY OBJECTIVES:

I. Compare whether adjuvant maintenance therapy comprising doxorubicin, cisplatin, and
high-dose methotrexate (MAP) alone vs MAP combined with ifosfamide and etoposide improves
event-free survival of patients with resectable high-grade osteosarcoma who achieve a poor
histological response (HR) to neoadjuvant induction therapy comprising MAP.

II. Compare whether adjuvant maintenance therapy comprising MAP alone vs MAP and
PEG-interferon alfa-2b improves event-free survival of patients with resectable high-grade
osteosarcoma who achieve a good HR to neoadjuvant induction therapy comprising MAP.

SECONDARY OBJECTIVES:

I. Compare overall survival of patients treated with these regimens. II. Compare short- and
long-term toxicity of these regimens in these patients. III. Compare quality of life of
patients treated with these regimens. IV. Compare event-free survival and overall survival
of patients with localized osteosarcoma treated with these regimens.

V. Correlate biological or clinical changes with histological response and outcomes in
patients treated with these regimens.

VI. Determine outcomes of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study.

INDUCTION THERAPY: (MAP; weeks 1-10) Patients receive doxorubicin IV continuously over 48
hours on days 1-2 and cisplatin IV over 4 hours on days 1 and 2 in weeks 1 and 6. Patients
also receive high-dose methotrexate (MTX)* IV over 4 hours on day 1 in weeks 4, 5, 9, and
10. Patients then proceed to surgery.

NOTE: *Patients must receive >= 2 but =< 6 doses of high-dose MTX.

SURGERY: Patients undergo amputation or limb salvage surgery in week 11. Tumor tissue is
evaluated for histological response to induction therapy. Patients whose tumor is not
amenable to macroscopically complete surgical resection undergo radiotherapy and/or other
investigational therapy off study. Patients who undergo macroscopically complete surgical
resection of the primary tumor or metastases AND who have no disease progression or
unacceptable toxicity proceed to maintenance therapy.

MAINTENANCE THERAPY: Patients are assigned to 1 of 2 groups according to histological
response (good [< 10% viable tumor] vs poor [≥ 10% viable tumor]). Patients in each group
are stratified according to site of primary tumor and presence of metastases.

GROUP 1: (good histological response) Patient are randomized to 1 of 2 treatment arms within
35 days after surgery.

ARM I: (MAP; weeks 12-29) Patients receive doxorubicin IV continuously over 48 hours on days
1-2 in weeks 12, 17, 22, and 26 and cisplatin IV over 4 hours on days 1 and 2 in weeks 12
and 17. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 16, 20,
21, 24, 25, 28, and 29.

ARM II: (MAPifn; weeks 12-104) Patients receive doxorubicin, cisplatin, and high-dose MTX as
in arm I. Patients than receive PEG-interferon alfa-2b subcutaneously once daily on day 1 in
weeks 30-104.

GROUP 2: (poor histological response) Patients are randomized to 1 of 2 treatment arms
within 35 days after surgery.

ARM I: (MAP; weeks 12-29) Patients receive doxorubicin, cisplatin, and high-dose MTX as in
group 1 arm I.

ARM II: (MAPIE; weeks 12-40) Patients receive doxorubicin IV continuously over 48 hours on
days 1-2 in weeks 12, 20, 28, and 36 and cisplatin IV over 4 hours on days 1 and 2 in weeks
12 and 28. Patients also receive high-dose MTX IV over 4 hours on day 1 in weeks 15, 19, 23,
27, 31, 35, 39, and 40. Patients receive ifosfamide IV over 4 hours on days 1-5 in weeks 16,
24, and 32 and on days 1-3 in weeks 20 and 36 and etoposide IV over 1 hour on days 1-5 in
weeks 16, 24, and 32.

In both groups, treatment continues in the absence of disease progression or unacceptable
toxicity. Quality of life is assessed periodically.

After completion of study treatment, patients are followed every 1½-3 months for 2 years,
every 2-4 months for 2 years, every 6 months for 6 years, and then every 6-12 months
thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK


Inclusion Criteria:



- Histologically confirmed high-grade osteosarcoma, including second malignancies

- Localized or metastatic disease

- The primary tumor must be located in the limbs or axial skeleton, including any
of the following sites*:

- Long bone of upper limb

- Short bone of upper limb

- Long bone of lower limb

- Short bone of lower limb

- Vertebral column

- Ribs, sternum, clavicle, or scapula

- Pelvic bones, sacrum, or coccyx

- Tumor (primary, metastatic, or both) resectable OR is expected to become resectable
after neoadjuvant induction chemotherapy

- Suitable for neoadjuvant chemotherapy

- Performance status - Lansky 50-100% (for patients under 16 years of age)

- Performance status - Karnofsky 50-100%*

- Performance status - WHO or ECOG 0-2*

- Platelet count ≥ 100,000/mm³

- Neutrophil count ≥ 1,500/mm³

- WBC ≥ 3,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal

- Creatinine clearance ≥ 70 mL/min

- Creatinine based on age as follows:

- No greater than 1.0 mg/dL (for patients 5 to 10 years of age)

- No greater than 1.2 mg/dL (for patients 11 to 15 years of age)

- No greater than 1.5 mg/dL (for patients over 15 years of age)

- Ejection fraction ≥ 50% by radionuclide angiogram

- Shortening fraction ≥ 28% by echocardiogram

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known HIV positivity

- No prior chemotherapy for any disease

- Prior radiotherapy for another malignancy allowed

- No prior treatment for osteosarcoma

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival

Outcome Description:

Will be assessed using the logrank test and expressed using hazard ratios with appropriate confidence intervals.

Outcome Time Frame:

From date of randomization to date of the event, assessed up to 10 years

Safety Issue:

No

Principal Investigator

Neyssa Marina

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

AOST0331

NCT ID:

NCT00134030

Start Date:

November 2005

Completion Date:

Related Keywords:

  • Localized Osteosarcoma
  • Metastatic Osteosarcoma
  • Osteosarcoma

Name

Location

Baylor College of MedicineHouston, Texas  77030
Johns Hopkins UniversityBaltimore, Maryland  21205
Cleveland Clinic FoundationCleveland, Ohio  44195
Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Geisinger Medical CenterDanville, Pennsylvania  17822-0001
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Massachusetts General Hospital Cancer CenterBoston, Massachusetts  02114
Marshfield ClinicMarshfield, Wisconsin  54449
Loma Linda University Medical CenterLoma Linda, California  92354
Baptist Hospital of MiamiMiami, Florida  33176-2197
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
Cedars-Sinai Medical CenterLos Angeles, California  90048
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Eastern Maine Medical CenterBangor, Maine  04401
William Beaumont HospitalRoyal Oak, Michigan  48073
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's National Medical CenterWashington, District of Columbia  20010-2970
All Children's HospitalSt. Petersburg, Florida  33701
Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Maine Children's Cancer ProgramScarborough, Maine  04074-9308
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health CenterPortland, Oregon  97227
Driscoll Children's HospitalCorpus Christi, Texas  78466
Scott and White Memorial HospitalTemple, Texas  76508
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Brooklyn Hospital CenterBrooklyn, New York  11201
Children's Hospital Medical Center of AkronAkron, Ohio  44308
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Overlook HospitalSummit, New Jersey  07902-0220
Mount Sinai Medical CenterNew York, New York  10029
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Montefiore Medical CenterBronx, New York  10467-2490
Saint Peter's University HospitalNew Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Children's Hospital and Research Center at OaklandOakland, California  94609-1809
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
City of Hope Medical CenterDuarte, California  91010
Presbyterian HospitalCharlotte, North Carolina  28233-3549
Lee Memorial Health SystemFort Myers, Florida  33902
University of VirginiaCharlottesville, Virginia  22908
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Connecticut Children's Medical CenterHartford, Connecticut  06106
University of North CarolinaChapel Hill, North Carolina  27599
Duke University Medical CenterDurham, North Carolina  27710
University of FloridaGainesville, Florida  32610-0277
University of RochesterRochester, New York  14642
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Yale UniversityNew Haven, Connecticut  06520
Wayne State UniversityDetroit, Michigan  48202
University of Arizona Health Sciences CenterTucson, Arizona  85724
University of Massachusetts Medical SchoolWorcester, Massachusetts  01605
Indiana University Medical CenterIndianapolis, Indiana  46202
University Of VermontBurlington,, Vermont  05403
Albany Medical CenterAlbany, New York  12208
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Oregon Health and Science UniversityPortland, Oregon  97201
Tulane University Health Sciences CenterNew Orleans, Louisiana  70112
Virginia Commonwealth UniversityRichmond, Virginia  
David Geffen School of Medicine at UCLALos Angeles, California  90095
Florida HospitalOrlando, Florida  32803
Memorial Health University Medical CenterSavannah, Georgia  31404
M D Anderson Cancer CenterHouston, Texas  77030
Seattle Children's HospitalSeattle, Washington  98105
Wake Forest University Health SciencesWinston-Salem, North Carolina  27157
Childrens Memorial HospitalChicago, Illinois  60614
Kaiser Permanente-OaklandOakland, California  94611
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
University of HawaiiHonolulu, Hawaii  96813
Saint Vincent Hospital and Health ServicesIndianapolis, Indiana  46260
Michigan State University - Breslin Cancer CenterEast Lansing, Michigan  48824-1313
Kalamazoo Center for Medical StudiesKalamazoo, Michigan  49008
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
Mission Hospitals IncAsheville, North Carolina  28801
Saint Vincent HospitalGreen Bay, Wisconsin  54301
University of IllinoisChicago, Illinois  60612
Cook Children's Medical CenterFort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's HospitalHollywood, Florida  33021
East Carolina UniversityGreenville, North Carolina  27858
The Children's Medical Center of DaytonDayton, Ohio  45404
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
Children's Oncology GroupArcadia, California  91006-3776
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
Cardinal Glennon Children's Medical CenterSt. Louis, Missouri  63104
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Phoenix Childrens HospitalPhoenix, Arizona  85016
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
The Childrens Mercy HospitalKansas City, Missouri  64108
Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
East Tennessee Childrens HospitalKnoxville, Tennessee  37916
Children's Hospital and Medical Center of OmahaOmaha, Nebraska  68114
Saint Joseph's Regional Medical CenterPaterson, New Jersey  07503
Texas Tech University Health Science Center-AmarilloAmarillo, Texas  79106
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Sanford Medical Center-FargoFargo, North Dakota  58122
Children's Hospital ColoradoAurora, Colorado  80045
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Raymond Blank Children's HospitalDes Moines, Iowa  50309
Children's Hospital-Main CampusNew Orleans, Louisiana  70118
Saint Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
Sanford USD Medical Center - Sioux FallsSioux Falls, South Dakota  57117-5134
T C Thompson Children's HospitalChattanooga, Tennessee  37403
Carilion Clinic Children's HospitalRoanoke, Virginia  24014
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204
The Steven and Alexandra Cohen Children's Medical Center of New YorkNew Hyde Park, New York  11040
Georgia Regents UniversityAugusta, Georgia  30912