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

Sarcoma Clinical Trial

Official title:

Treatment of Newly Diagnosed Untreated Osteosarcoma: A Pilot Study of a New Chemotherapeutic Regimen Including Ifosfamide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00645632
• Other study ID #: CDR0000582263
• Secondary ID: P30CA01508390910
• Status: Completed
• Phase: N/A
• First received: March 26, 2008
• Last updated: May 13, 2011
• Start date: November 1990
• Est. completion date: January 2008

Study information

• Verified date: May 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 2008
• Est. primary completion date: January 1995
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Osteosarcoma
• Sarcoma

Intervention

Drug:
• cisplatin

• doxorubicin hydrochloride

• ifosfamide

• methotrexate

Procedure:
• adjuvant therapy

• neoadjuvant therapy

• therapeutic conventional surgery

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histopathologic response rate			No
Primary	Clinical response rate			No
Primary	Toxicity			Yes
Primary	Disease-free survival			No
Primary	Overall survival			No