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

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00645632

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

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Doxorubicin Doxorubicin hydrochloride Ifosfamide Cisplatin Methotrexate

U.S. FDA Resources

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

Further study details as provided by National Cancer Institute (NCI):

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
Primary Completion Date:	January 2008 (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

National Cancer Institute (NCI)

Investigators

Investigator:	Robert F. Marschke, MD	Mayo Clinic Scottsdale
Study Chair:	Gerald S. Gilchrist, MD	Mayo Clinic

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000582263, MAYO-909101
Study First Received:	March 26, 2008
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00645632
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

localized osteosarcoma

Study placed in the following topic categories:

Malignant mesenchymal tumor
Osteosarcoma
Osteogenic sarcoma
Soft tissue sarcomas
Doxorubicin
Folic Acid
Neoplasms, Connective and Soft Tissue

Ifosfamide
Cisplatin
Mechlorethamine
Sarcoma
Methotrexate
Isophosphamide mustard

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Reproductive Control Agents
Folic Acid Antagonists
Antibiotics, Antineoplastic
Abortifacient Agents, Nonsteroidal

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Neoplasms, Bone Tissue
Therapeutic Uses
Abortifacient Agents
Neoplasms, Connective Tissue
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Alkylating Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 15, 2009