Combination Chemotherapy in Treating Patients Undergoing Surgery for Newly Diagnosed High-Grade Osteosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00645632
Recruitment Status : Completed
First Posted : March 27, 2008
Last Update Posted : May 16, 2011
National Cancer Institute (NCI)
Information provided by:
Mayo Clinic

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as ifosfamide, methotrexate, cisplatin, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating patients undergoing surgery for newly diagnosed high-grade osteosarcoma.

Condition or disease Intervention/treatment Phase
Sarcoma Drug: cisplatin Drug: doxorubicin hydrochloride Drug: ifosfamide Drug: methotrexate Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: therapeutic conventional surgery Not Applicable

Detailed Description:


  • To evaluate the efficacy of a new induction regimen comprising ifosfamide in combination with high-dose methotrexate, cisplatin, and doxorubicin hydrochloride, in terms of clinical response and pathological response of the tumor, in patients with newly diagnosed high-grade osteosarcoma.
  • To determine the overall survival and disease-free survival of these patients.
  • To evaluate the toxicity of this regimen.
  • To correlate MRI imaging of the primary tumor with histopathologic grading after treatment with this regimen.

OUTLINE: This is a multicenter study.

  • Neoadjuvant chemotherapy (weeks 1-15): Patients receive ifosfamide IV over 1 hour on days 1-5 and 36-40; doxorubicin hydrochloride IV over 18 hours on days 1-3 and 36-38 and IV over 72 hours on days 71-73; high-dose methotrexate IV over 4 hours on days 22, 29, 57, 64, 92, and 99; and cisplatin IV over 4 hours on day 71.
  • Surgery (week 16): Patients undergo resection of the tumor on day 106. Patients found to have unresectable disease are treated on an alternative protocol unless they have clear clinical and pathologic response to treatment.
  • Adjuvant chemotherapy (weeks 18-43): Beginning 2 weeks after surgery, patients receive ifosfamide IV over 1 hour on days 120-124, 155-159, 225-229, and 260-264; doxorubicin hydrochloride IV over 18 hours on days 120-122 and 155-157 and IV over 72 hours on days 190-192; high-dose methotrexate IV over 4 hours on days 141, 148, 176, 183, 211, 218, 246, 253, 281, and 288; and cisplatin IV over 4 hours on days 190 and 289.

After completion of study therapy, patients are followed every 2 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Primary Purpose: Treatment
Official Title: Treatment of Newly Diagnosed Untreated Osteosarcoma: A Pilot Study of a New Chemotherapeutic Regimen Including Ifosfamide
Study Start Date : November 1990
Actual Primary Completion Date : January 1995
Actual Study Completion Date : January 2008

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Histopathologic response rate
  2. Clinical response rate
  3. Toxicity
  4. Disease-free survival
  5. Overall survival

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed osteosarcoma of the extremity

    • High-grade (grade III or IV) disease

      • No low-grade disease (e.g., parosteal or periosteal osteosarcoma)
  • No secondary osteosarcoma (i.e., tumor occurring in a radiotherapy field designed for a prior tumor)
  • No Paget's disease
  • No known metastases


  • Total bilirubin < 2 times normal
  • AST < 2 times normal
  • Alkaline phosphatase < 2 times normal
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance > 60 mL/min
  • LVEF ≥ 45%
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No other prior malignancy except retinoblastoma

    • Patients with familial retinoblastoma syndrome who develop osteosarcoma unrelated to radiotherapy (e.g., in a primary site in the extremities) are eligible


  • No prior chemotherapy or radiotherapy

    • Patients with retinoblastoma may have received radiotherapy to the orbits
  • At least 28 days since prior initial amputation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00645632

Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Gerald S. Gilchrist, MD Mayo Clinic
Principal Investigator: Tom R Fitch, M.D. Mayo Clinic
Principal Investigator: Gerardo Colon-Otero, M.D. Mayo Clinic Florida

Responsible Party: Carola A.S. Arndt, Mayo Clinic Identifier: NCT00645632     History of Changes
Other Study ID Numbers: CDR0000582263
P30CA015083 ( U.S. NIH Grant/Contract )
909101 ( Other Identifier: Mayo Clinic Cancer Center )
549-90 ( Other Identifier: Mayo Clinic IRB )
First Posted: March 27, 2008    Key Record Dates
Last Update Posted: May 16, 2011
Last Verified: May 2011

Keywords provided by Mayo Clinic:
localized osteosarcoma

Additional relevant MeSH terms:
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Liposomal doxorubicin
Isophosphamide mustard
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Dermatologic Agents
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors