Zoledronic Acid and Combination Chemotherapy in Treating Patients With Newly Diagnosed Metastatic Osteosarcoma

June 4, 2014 updated by: Children's Oncology Group

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

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.

Study Overview

Detailed Description

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 at the assigned dose level over 30 minutes on day 4 of weeks 1 and 6; high-dose methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and 10; leucovorin calcium IV or orally every 6 hours starting on day 2 and continuing until clearance of methotrexate of weeks 4, 5, 9, and 10; and filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 3 of weeks 1 and 6 and continuing until blood counts recover.
  • Surgery (week 12): Patients undergo definitive surgery (limb-salvage surgery or amputation) of the primary tumor in week 12.
  • Maintenance therapy course 1 (weeks 13-25): Patients receive etoposide IV over 1 hour and ifosfamide IV over 4 hours on days 1-5 of weeks 13 and 21; zoledronic acid IV over 30 minutes on day 4 of week 17 and on day 7 of weeks 13 and 21; high-dose methotrexate IV over 4 hours on day 1 of weeks 16, 20, and 24; leucovorin calcium IV or orally every 6 hours starting on day 2 and continuing until clearance of methotrexate of weeks 16, 20, and 24; dexrazoxane hydrochloride IV slowly over 5-15 minutes, doxorubicin hydrochloride IV over 15 minutes, and cisplatin IV over 1 hour on days 1 and 2 of week 17; and G-CSF SC once daily beginning on day 6 of weeks 13, 17, and 21 and continuing until blood counts recover.
  • Surgery (week 26): Patients may undergo surgical resection of primary metastases in week 26.
  • Maintenance therapy course 2 (weeks 27-36): Patients receive dexrazoxane hydrochloride IV slowly over 5-15 minutes and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 of weeks 27 and 31; cisplatin IV over 1 hour on days 1 and 2 of week 27; zoledronic acid IV over 30 minutes on day 4 of week 27 and on day 7 of weeks 31 and 36; high-dose methotrexate IV over 4 hours on day 1 of weeks 30, 34, and 35; leucovorin calcium IV or orally every 6 hours starting on day 2 and continuing until clearance of methotrexate of weeks 30, 34, and 35; etoposide IV over 1 hour on days 1-5 of week 36; ifosfamide (1.8 gm/m2 ) IV over 1 hour on days 1-5 of week 31;ifosfamide (2.8 gm/m2)IV over 4 hours on days 1-5 of week 36; and G-CSF SC once daily beginning on day 3 of weeks 27, 31, and 36 and continuing until blood counts recover.

Mensa is a supportive care medicine used to prevent hemorrhagic cystitis caused by ifosfamide. It is always given when ifosfamide is given. It was used in all arms.

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

Study Type

Interventional

Enrollment (Actual)

24

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Western Australia
      • Perth, Western Australia, Australia, 6001
        • Princess Margaret Hospital for Children
    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
    • British Columbia
      • Vancouver, British Columbia, Canada, V6H 3V4
        • Children's & Women's Hospital of British Columbia
    • Manitoba
      • Winnipeg, Manitoba, Canada, R3E 0V9
        • CancerCare Manitoba
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
        • Janeway Children's Health and Rehabilitation Centre
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3K 6R8
        • IWK Health Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster Children's Hospital at Hamilton Health Sciences
      • Toronto, Ontario, Canada, M5G 1X8
        • Hospital For Sick Children
    • Quebec
      • Montreal, Quebec, Canada, H3T 1C5
        • Hopital Sainte Justine
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 4H4
        • Saskatoon Cancer Centre at the University of Saskatchewan
      • Santurce, Puerto Rico, 00912
        • San Jorge Children's Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Uab Comprehensive Cancer Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
    • California
      • Downey, California, United States, 90027
        • Southern California Permanente Medical Group
      • Long Beach, California, United States, 90801
        • Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
      • Los Angeles, California, United States, 90027
        • Childrens Hospital Los Angeles
      • Madera, California, United States, 93638-8762
        • Children's Hospital Central California
      • Oakland, California, United States, 94609
        • Children's Hospital and Research Center Oakland
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County
      • Palo Alto, California, United States, 94304
        • Lucile Packard Children's Hospital Stanford University
      • San Diego, California, United States, 92123-4282
        • Rady Children's Hospital - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Connecticut
      • Farmington, Connecticut, United States, 06360-2875
        • Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I. DuPont Hospital for Children
    • District of Columbia
      • Washington, District of Columbia, United States, 20010-2970
        • Children's National Medical Center
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Nemours Children's Clinic
      • Orlando, Florida, United States, 32806
        • Nemours Children's Clinic - Orlando
      • Pensacola, Florida, United States, 32504
        • Sacred Heart Cancer Center at Sacred Heart Hospital
      • Saint Petersburg, Florida, United States, 33701
        • All Children's Hospital
      • Tampa, Florida, United States, 33607
        • St. Joseph's Cancer Institute at St. Joseph's Hospital
      • West Palm Beach, Florida, United States, 33407
        • Kaplan Cancer Center at St. Mary's Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Cancer Research Center of Hawaii
    • Idaho
      • Boise, Idaho, United States, 83712-6297
        • Mountain States Tumor Institute at St. Luke's Regional Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Children's Memorial Hospital - Chicago
      • Oak Lawn, Illinois, United States, 60453
        • Keyser Family Cancer Center at Advocate Hope Children's Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5289
        • Indiana University Melvin and Bren Simon Cancer Center
    • Iowa
      • Iowa City, Iowa, United States, 52242-1002
        • Holden Comprehensive Cancer Center at University of Iowa
    • Kansas
      • Kansas City, Kansas, United States, 66160-7357
        • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kentucky
      • Lexington, Kentucky, United States, 40536-0093
        • Lucille P. Markey Cancer Center at University of Kentucky
      • Louisville, Kentucky, United States, 40232
        • Kosair Children's Hospital
    • Maine
      • Scarborough, Maine, United States, 04074-9308
        • Maine Children's Cancer Program at Barbara Bush Children's Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21215
        • Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0286
        • C.S. Mott Children's Hospital at University of Michigan Medical Center
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Grand Rapids, Michigan, United States, 49503-2560
        • Butterworth Hospital at Spectrum Health
      • Kalamazoo, Michigan, United States, 49007-5381
        • CCOP - Kalamazoo
      • Lansing, Michigan, United States, 48910
        • Breslin Cancer Center at Ingham Regional Medical Center
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center at University of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • Mississippi
      • Jackson, Mississippi, United States, 39216-4505
        • University of Mississippi Cancer Clinic
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Children's Mercy Hospital
      • St. Louis, Missouri, United States, 63110
        • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center Cancer Center
      • Morristown, New Jersey, United States, 07962
        • Overlook Hospital
      • New Brunswick, New Jersey, United States, 08903
        • Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131-5636
        • University of New Mexico Cancer Center
    • New York
      • New York, New York, United States, 10016
        • NYU Cancer Institute at New York University Medical Center
      • New York, New York, United States, 10032
        • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
      • Syracuse, New York, United States, 13210
        • SUNY Upstate Medical University Hospital
    • North Carolina
      • Charlotte, North Carolina, United States, 28232-2861
        • Blumenthal Cancer Center at Carolinas Medical Center
      • Charlotte, North Carolina, United States, 28233-3549
        • Presbyterian Cancer Center at Presbyterian Hospital
      • Durham, North Carolina, United States, 27710
        • Duke Comprehensive Cancer Center
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • Ohio
      • Akron, Ohio, United States, 44308-1062
        • Akron Children's Hospital
      • Cincinnati, Ohio, United States, 45229-3039
        • Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Taussig Cancer Center
      • Cleveland, Ohio, United States, 44106-5000
        • Rainbow Babies and Children's Hospital
      • Columbus, Ohio, United States, 43205-2696
        • Nationwide Children's Hospital
      • Dayton, Ohio, United States, 45404-1815
        • Dayton Children's - Dayton
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Cancer Institute
    • Oregon
      • Portland, Oregon, United States, 97239-3098
        • Knight Cancer Institute at Oregon Health and Science University
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033-0850
        • Penn State Children's Hospital
    • South Carolina
      • Columbia, South Carolina, United States, 29203
        • Palmetto Health South Carolina Cancer Center
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • T.C. Thompson Children's Hospital
      • Knoxville, Tennessee, United States, 37901
        • East Tennessee Children's Hospital
    • Texas
      • Corpus Christi, Texas, United States, 78411
        • Driscoll Children's Hospital
      • Dallas, Texas, United States, 75230
        • Medical City Dallas Hospital
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • San Antonio, Texas, United States, 78229-3993
        • Methodist Children's Hospital of South Texas
      • San Antonio, Texas, United States, 78207
        • University of Texas Health Science Center at San Antonio
    • Utah
      • Salt Lake City, Utah, United States, 84113-1100
        • Primary Children's Medical Center
    • Virginia
      • Norfolk, Virginia, United States, 23507-1971
        • Children's Hospital of The King's Daughters
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hospital and Regional Medical Center - Seattle
      • Spokane, Washington, United States, 99220-2555
        • Providence Cancer Center at Sacred Heart Medical Center
    • West Virginia
      • Charleston, West Virginia, United States, 25302
        • West Virginia University Health Sciences Center - Charleston
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic - Marshfield Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 40 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 contraception
  • No known HIV infection
  • No history of pericarditis, myocarditis, symptomatic arrhythmia, or conduction disturbances

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy
  • No other concurrent anticancer chemotherapy
  • No concurrent immunomodulating agents
  • Steroids for anti-emetic allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.

Given IV
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Given IV
Other Names:
  • VP-16
  • Etopophos
  • VePesid
  • NSC #141540
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Given IV
Other Names:
  • ADR-529
  • ICRF-187
  • ZINECARD
  • NSC #169780
Given SC
Other Names:
  • G-CSF
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • Neupogen
  • NSC #614629
Given IV
Other Names:
  • CDDP
  • Platinol-AQ
  • cis-DDP
  • Cis-diamminedichloroplatinum II
  • NSC #119875
Given IV or orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Given IV
Other Names:
  • Mesnex
  • UCB 3983
  • sodium 2-mercaptoethane sulfonate
  • NSC #113891
Given IV
Other Names:
  • Zometa
  • zoledronate
  • Aclasta
  • 1-Hydroxy-2-imidazol-1-ylethylidene - diphosphonic acid
  • NSC# 721517
Given IV
Other Names:
  • Ifex
  • Iphosphamide
  • Isophosphamide
  • Z4942
  • NSC #109724
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
Experimental: 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.

Given IV
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Given IV
Other Names:
  • VP-16
  • Etopophos
  • VePesid
  • NSC #141540
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Given IV
Other Names:
  • ADR-529
  • ICRF-187
  • ZINECARD
  • NSC #169780
Given SC
Other Names:
  • G-CSF
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • Neupogen
  • NSC #614629
Given IV
Other Names:
  • CDDP
  • Platinol-AQ
  • cis-DDP
  • Cis-diamminedichloroplatinum II
  • NSC #119875
Given IV or orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Given IV
Other Names:
  • Mesnex
  • UCB 3983
  • sodium 2-mercaptoethane sulfonate
  • NSC #113891
Given IV
Other Names:
  • Zometa
  • zoledronate
  • Aclasta
  • 1-Hydroxy-2-imidazol-1-ylethylidene - diphosphonic acid
  • NSC# 721517
Given IV
Other Names:
  • Ifex
  • Iphosphamide
  • Isophosphamide
  • Z4942
  • NSC #109724
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
Experimental: 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.

Given IV
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Given IV
Other Names:
  • VP-16
  • Etopophos
  • VePesid
  • NSC #141540
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Given IV
Other Names:
  • ADR-529
  • ICRF-187
  • ZINECARD
  • NSC #169780
Given SC
Other Names:
  • G-CSF
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • Neupogen
  • NSC #614629
Given IV
Other Names:
  • CDDP
  • Platinol-AQ
  • cis-DDP
  • Cis-diamminedichloroplatinum II
  • NSC #119875
Given IV or orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Given IV
Other Names:
  • Mesnex
  • UCB 3983
  • sodium 2-mercaptoethane sulfonate
  • NSC #113891
Given IV
Other Names:
  • Zometa
  • zoledronate
  • Aclasta
  • 1-Hydroxy-2-imidazol-1-ylethylidene - diphosphonic acid
  • NSC# 721517
Given IV
Other Names:
  • Ifex
  • Iphosphamide
  • Isophosphamide
  • Z4942
  • NSC #109724
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.
Experimental: 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.

Given IV
Other Names:
  • amethopterin
  • MTX
  • NSC #000740
  • Trexall
Given IV
Other Names:
  • VP-16
  • Etopophos
  • VePesid
  • NSC #141540
Given IV
Other Names:
  • Adriamycin
  • NSC #123127
Given IV
Other Names:
  • ADR-529
  • ICRF-187
  • ZINECARD
  • NSC #169780
Given SC
Other Names:
  • G-CSF
  • Granulocyte Colony-Stimulating Factor
  • r-metHuG-CSF
  • Neupogen
  • NSC #614629
Given IV
Other Names:
  • CDDP
  • Platinol-AQ
  • cis-DDP
  • Cis-diamminedichloroplatinum II
  • NSC #119875
Given IV or orally
Other Names:
  • LCV
  • Wellcovorin
  • citrovorum factor
  • folinic acid
  • NSC #003590
Given IV
Other Names:
  • Mesnex
  • UCB 3983
  • sodium 2-mercaptoethane sulfonate
  • NSC #113891
Given IV
Other Names:
  • Zometa
  • zoledronate
  • Aclasta
  • 1-Hydroxy-2-imidazol-1-ylethylidene - diphosphonic acid
  • NSC# 721517
Given IV
Other Names:
  • Ifex
  • Iphosphamide
  • Isophosphamide
  • Z4942
  • NSC #109724
Surgery of the primary tumor is scheduled for 12 weeks after the commencement of chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Limiting Toxicity
Time Frame: Enrollment through the first 12 weeks of therapy.

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:

  • Grade 3 nausea and vomiting controlled with adequate antiemetic prophylaxis.
  • Grade 3 transaminase (AST/ALT) that occurs during the evaluation period but resolves to ≤ Grade 2, before the planned dose of therapy after definitive surgery.
  • Grade 3 fever or infection.
  • Grade 3 or 4 hypocalcemia (see Section 5.1.1)
  • Grade 3 mucositis.
  • Grade 3 fatigue that returns to ≤ Grade 2, before the planned dose of therapy after definitive surgery.
  • Grade 3 joint range of motion, decreased or joint effusion that is related to the primary tumor.
Enrollment through the first 12 weeks of therapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histologic Response as Assessed in the Primary Tumor and in Resected Metastases
Time Frame: At definitive surgery planned for 12 weeks after the start of protocol therapy.

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.

At definitive surgery planned for 12 weeks after the start of protocol therapy.
Event-free Survival
Time Frame: Time from study enrollment to disease recurrence, death without disease progression, diagnosis of a second malignant neoplasm, assessed up to 5 years
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
Time Frame: After week 13 to the end of protocol therapy

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:

  • Grade 3 nausea and vomiting controlled with adequate antiemetic prophylaxis.
  • Grade 3 transaminase (AST/ALT) that occurs during the evaluation period but resolves to ≤ Grade 2, before the planned dose of therapy after definitive surgery.
  • Grade 3 fever or infection.
  • Grade 3 or 4 hypocalcemia (see Section 5.1.1)
  • Grade 3 mucositis.
  • Grade 3 fatigue that returns to ≤ Grade 2, before the planned dose of therapy after definitive surgery.
  • Grade 3 joint range of motion, decreased or joint effusion that is related to the primary tumor.

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
Time Frame: At baseline and at weeks 13 and 36
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Robert Goldsby, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2008

Primary Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

August 27, 2008

First Submitted That Met QC Criteria

August 27, 2008

First Posted (Estimate)

August 28, 2008

Study Record Updates

Last Update Posted (Estimate)

July 4, 2014

Last Update Submitted That Met QC Criteria

June 4, 2014

Last Verified

June 1, 2014

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sarcoma

Clinical Trials on adjuvant therapy

3
Subscribe