Combination Chemotherapy Before and After Surgery in Treating Patients With Osteosarcoma

June 4, 2015 updated by: National Cancer Institute (NCI)

Osteosarcoma: Outcome of Therapy Based on Histologic Response. A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma.

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy before surgery may shrink the tumor so that it can be removed during surgery. Giving chemotherapy after surgery may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving chemotherapy before and after surgery works in treating patients with osteosarcoma.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the rate of in vivo histologic response in patients with osteosarcoma treated with neoadjuvant cisplatin, methotrexate, and doxorubicin with dexrazoxane (as cardioprotection).
  • Determine the event-free and overall survival of patients with nonmetastatic disease who show good response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
  • Determine the event-free survival of patients with nonmetastatic disease who show poor response to neoadjuvant therapy and receive adjuvant therapy with the same regimen.
  • Determine the event-free survival and overall survival of patients with metastatic disease who receive neoadjuvant therapy.

OUTLINE: This is a multicenter study.

  • Neoadjuvant therapy: Patients receive neoadjuvant chemotherapy comprising dexrazoxane IV over 15 minutes, doxorubicin IV over 15 minutes, and cisplatin IV over 4 hours on days 1 and 2 in week 0. Patients also receive methotrexate IV over 4 hours followed by leucovorin calcium in weeks 3 and 4. Patients then receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning 24 hours after completion of chemotherapy and continuing until blood counts recover. Treatment repeats every 5 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
  • Surgical resection: Patients undergo definitive surgery in week 11.
  • Adjuvant therapy: Patients receive dexrazoxane, doxorubicin, cisplatin, methotrexate, and leucovorin calcium as in neoadjuvant therapy*. Treatment repeats every 5 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Cisplatin is not administered in courses 3 and 4 of adjuvant therapy

Patients are followed within 4 weeks, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: Approximately 100 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 2

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

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892-1182
        • Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Oklahoma University Cancer Institute
    • Texas
      • Fort Worth, Texas, United States, 76104
        • Cook Children's Medical Center - Fort Worth
      • Houston, Texas, United States, 77030-2399
        • Texas Children's Cancer Center and Hematology Service at Texas Children's Hospital

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 25 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed newly diagnosed osteosarcoma

    • No more than 1 month since prior diagnostic biopsy
    • Nonmetastatic malignant high-grade osteosarcoma of bone
    • Histologically confirmed metastatic disease allowed
    • Unresectable primary disease allowed
  • No low-grade, parosteal, or periosteal osteosarcoma

PATIENT CHARACTERISTICS:

Age:

  • 25 and under

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8.0 g/dL

Hepatic:

  • Bilirubin no greater than 2.0 mg/dL
  • ALT less than 5 times normal

Renal:

  • Creatinine no greater than 1.5 times normal
  • Creatinine clearance or radioisotope glomerular filtration rate greater than 70 mL/min

Cardiovascular:

  • Shortening fraction at least 27% by echocardiogram or MUGA
  • Ejection fraction at least 45% by echocardiogram or MUGA

Other:

  • Not pregnant
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 6 months after study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • See Disease Characteristics
  • No other concurrent chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • See Disease Characteristics

Surgery:

  • Not specified

Other:

  • No other concurrent therapy with no evidence of progressive disease

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
  • Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival
Event-free survival
Rate of in vivo histologic response

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Study Chair: Ramzi Dagher, MD, National Cancer Institute (NCI)

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

March 1, 2000

Primary Completion (ACTUAL)

December 1, 2006

Study Completion (ACTUAL)

October 1, 2011

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

June 8, 2015

Last Update Submitted That Met QC Criteria

June 4, 2015

Last Verified

October 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000067263
  • NCI-99-C-0125I

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.

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