Know Cancer

or
forgot password

Feasibility and Dose Discovery Analysis of Zoledronic Acid With Concurrent Chemotherapy in the Treatment of Newly Diagnosed Metastatic Osteosarcoma


N/A
N/A
40 Years
Not Enrolling
Both
Sarcoma

Thank you

Trial Information

Feasibility and Dose Discovery Analysis of Zoledronic Acid With Concurrent Chemotherapy in the Treatment of Newly Diagnosed Metastatic Osteosarcoma


OBJECTIVES:

Primary

- To assess the feasibility and safety of zoledronic acid when administered in
combination with standard chemotherapy in patients with newly diagnosed metastatic
osteosarcoma.

- To determine the maximum tolerated dose of zoledronic acid when administered in
combination with standard chemotherapy in these patients.

Secondary

- To compare the histologic response and event-free survival of patients treated with
this regimen versus patients treated on INT-0133 or CCG-7943.

OUTLINE: This is a multicenter, dose-escalation study of zoledronic acid.

- Induction therapy (weeks 1-11): Patients receive dexrazoxane hydrochloride IV slowly
over 5-15 minutes, doxorubicin hydrochloride IV over 15 minutes, and cisplatin IV over
1 hour on days 1 and 2 of weeks 1 and 6; zoledronic acid IV over 30 minutes on day 4 of
weeks 1 and 6; high-dose methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and
10; leucovorin calcium IV or orally every 6 hours on day 2 of weeks 4, 5, 9, and 10;
and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 of weeks 1 and
6 and continuing until blood counts recover.

- Surgery (week 12): Patients undergo definitive surgery (limb-salvage surgery or
amputation) of the primary tumor in week 12.

- Maintenance therapy course 1 (weeks 13-25): Patients receive etoposide IV over 1 hour
and ifosfamide IV over 4 hours on days 1-5 of weeks 13 and 21; zoledronic acid IV over
30 minutes on day 4 of week 17 and on day 7 of weeks 13 and 21; high-dose methotrexate
IV over 4 hours on day 1 of weeks 16, 20, and 24; leucovorin calcium IV or orally every
6 hours on day 2 of weeks 16, 20, and 24; dexrazoxane hydrochloride IV slowly over 5-15
minutes, doxorubicin hydrochloride IV over 15 minutes, and cisplatin IV over 1 hour on
days 1 and 2 of week 17; and G-CSF SC once daily beginning on day 6 of weeks 13, 17,
and 21 and continuing until blood counts recover.

- Surgery (week 26): Patients may undergo surgical resection of primary metastases in
week 26.

- Maintenance therapy course 2 (weeks 27-36): Patients receive dexrazoxane hydrochloride
IV slowly over 5-15 minutes and doxorubicin hydrochloride IV over 15 minutes on days 1
and 2 of weeks 27 and 31; cisplatin IV over 1 hour on days 1 and 2 of week 27;
zoledronic acid IV over 30 minutes on day 4 of week 27 and on day 7 of weeks 31 and 36;
high-dose methotrexate IV over 4 hours on day 1 of weeks 30, 34, and 35; leucovorin
calcium IV or orally every 6 hours on day 2 of weeks 30, 34, and 35; etoposide IV over
1 hour on days 1-5 of week 36; low-dose ifosfamide IV over 1 hour on days 1-5 of week
31; standard-dose ifosfamide IV over 4 hours on days 1-5 of week 36; and G-CSF SC once
daily beginning on day 3 of weeks 27, 31, and 36 and continuing until blood counts
recover.

After completion of study treatment, patients are followed periodically for up to 5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Biopsy-proven high-grade osteosarcoma within the past 6 weeks

- Newly diagnosed disease

- Metastatic disease

- Resectable disease OR expected to become resectable after initial chemotherapy

- Disease has arisen outside of areas of Paget's disease

PATIENT CHARACTERISTICS:

- ECOG performance status (PS) 0-2 OR Karnofsky PS 50-100% (for patients > 16 years of
age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR
maximum serum creatinine based on age/gender as follows:

- 0.4 mg/dL (for patients 1 to 5 months of age)

- 0.5 mg/dL (for patients 6 to 11 months of age)

- 0.6 mg/dL (for patients 1 year of age)

- 0.8 mg/dL (for patients 2 to 5 years of age)

- 1 mg/dL (for patients 6 to 9 years of age)

- 1.2 mg/dL (for patients 10 to 12 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients ≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- AST or ALT < 2.5 times ULN for age

- Shortening fraction ≥ 28% by echocardiogram OR ejection fraction ≥ 50% by
radionuclide angiogram

- ANC ≥ 1,000/mm³

- Platelet count ≥ 100,000/mm³ (transfusion independent)

- Hemoglobin ≥ 10 g/dL (RBC transfusion allowed)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No known HIV infection

- No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction
disturbances

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy or radiotherapy

- No concurrent sodium bicarbonate

- No other concurrent anticancer chemotherapy

- No concurrent immunomodulating agents, including steroids

- Corticosteroids for increased intracranial pressure allowed for patients with
CNS tumors

- Steroids for anti-emetic allowed

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and feasibility of zoledronic acid combined with chemotherapy regimen as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Outcome Description:

Descriptive statistics will be utilized to assess feasibility and safety.

Outcome Time Frame:

Up to 12 weeks

Safety Issue:

Yes

Principal Investigator

Robert Goldsby, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco

Authority:

United States: Federal Government

Study ID:

AOST06P1

NCT ID:

NCT00742924

Start Date:

August 2008

Completion Date:

Related Keywords:

  • Sarcoma
  • metastatic osteosarcoma
  • Osteosarcoma
  • Sarcoma

Name

Location

Mayo Clinic Cancer CenterRochester, Minnesota  55905
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
CCOP - KalamazooKalamazoo, Michigan  49007-3731
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
Cancer Research Center of HawaiiHonolulu, Hawaii  96813
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Children's Hospital of Orange CountyOrange, California  92668
Children's National Medical CenterWashington, District of Columbia  20010-2970
Children's Mercy HospitalKansas City, Missouri  64108
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Nemours Children's ClinicJacksonville, Florida  32207
All Children's HospitalSt. Petersburg, Florida  33701
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Driscoll Children's HospitalCorpus Christi, Texas  78466
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Overlook HospitalSummit, New Jersey  07902-0220
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Breslin Cancer Center at Ingham Regional Medical CenterLansing, Michigan  48910
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
Childrens Hospital Los AngelesLos Angeles, California  90027
Children's Hospital and Research Center OaklandOakland, California  94609
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
UCSF Helen Diller Family Comprehensive Cancer CenterSan Francisco, California  94115
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoise, Idaho  83712-6297
Keyser Family Cancer Center at Advocate Hope Children's HospitalOak Lawn, Illinois  60453
Indiana University Melvin and Bren Simon Cancer CenterIndianapolis, Indiana  46202-5289
Lucille P. Markey Cancer Center at University of KentuckyLexington, Kentucky  40536-0093
Maine Children's Cancer Program at Barbara Bush Children's HospitalScarborough, Maine  04074-9308
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer InstituteBoston, Massachusetts  02115
C.S. Mott Children's Hospital at University of Michigan Medical CenterAnn Arbor, Michigan  48109-0286
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Masonic Cancer Center at University of MinnesotaMinneapolis, Minnesota  55455
University of Mississippi Cancer ClinicJackson, Mississippi  39216-4505
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Akron Children's HospitalAkron, Ohio  44308-1062
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Dayton Children's - DaytonDayton, Ohio  45404-1815
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Knight Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97239-3098
Penn State Children's HospitalHershey, Pennsylvania  17033-0850
West Virginia University Health Sciences Center - CharlestonCharleston, West Virginia  25302
UAB Comprehensive Cancer CenterBirmingham, Alabama  35294
Stanford Cancer CenterStanford, California  94305-5824
T.C. Thompson Children's HospitalChattanooga, Tennessee  37403