Combination Chemotherapy Before and After Surgery in Treating Patients With Osteosarcoma - Full Text View

Sponsor:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00019864

Purpose

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.

Condition	Intervention	Phase
Cardiac Toxicity Sarcoma	Biological: filgrastim Drug: cisplatin Drug: dexrazoxane hydrochloride Drug: doxorubicin hydrochloride Drug: leucovorin calcium Drug: methotrexate Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Osteosarcoma: Outcome of Therapy Based on Histologic Response. A Collaborative Effort of the POB/NCI, Texas Children's Hospital and University of Oklahoma.

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma Surgery

Drug Information available for: Leucovorin Methotrexate Cisplatin Razoxane Doxorubicin Dexrazoxane Doxorubicin hydrochloride Citrovorum factor Myocet Filgrastim Dexrazoxane hydrochloride Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

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

Primary Outcome Measures:

Rate of in vivo histologic response [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	March 2000
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	up to 25 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019864

Locations

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

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Ramzi Dagher, MD

NCI - Pediatric Oncology Branch

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000067263, NCI-99-C-0125I
Study First Received:	July 11, 2001
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00019864 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

cardiac toxicity
localized osteosarcoma
metastatic osteosarcoma
recurrent osteosarcoma

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leucovorin
Reproductive Control Agents
Antibiotics, Antineoplastic
Razoxane
Neoplasms, Connective and Soft Tissue
Cisplatin
Therapeutic Uses
Vitamins
Abortifacient Agents

Methotrexate
Micronutrients
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Vitamin B Complex
Growth Substances
Osteosarcoma
Enzyme Inhibitors
Cardiovascular Agents
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009