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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00645632
First received: March 26, 2008
Last updated: May 13, 2011
Last verified: May 2011
  Purpose

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 Intervention
Sarcoma
Drug: cisplatin
Drug: doxorubicin hydrochloride
Drug: ifosfamide
Drug: methotrexate
Procedure: adjuvant therapy
Procedure: neoadjuvant therapy
Procedure: therapeutic conventional surgery

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Treatment of Newly Diagnosed Untreated Osteosarcoma: A Pilot Study of a New Chemotherapeutic Regimen Including Ifosfamide

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Histopathologic response rate [ Designated as safety issue: No ]
  • Clinical response rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
  • Disease-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: November 1990
Study Completion Date: January 2008
Primary Completion Date: January 1995 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy or radiotherapy

    • Patients with retinoblastoma may have received radiotherapy to the orbits
  • At least 28 days since prior initial amputation
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00645632

Sponsors and Collaborators
Mayo Clinic
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Carola A.S. Arndt, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00645632     History of Changes
Other Study ID Numbers: CDR0000582263, P30CA015083, 909101, 549-90
Study First Received: March 26, 2008
Last Updated: May 13, 2011
Health Authority: United States: Federal Government

Keywords provided by Mayo Clinic:
localized osteosarcoma

Additional relevant MeSH terms:
Osteosarcoma
Sarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Isophosphamide mustard
Cisplatin
Doxorubicin
Ifosfamide
Methotrexate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on April 23, 2014