Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Neoadjuvant and Adjuvant Pamidronate With Induction and Maintenance Chemotherapy in Treating Patients With Osteosarcoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed Any age NCI MSKCC-03074 NCT00072306

Objectives

1. Determine the safety and feasibility of pamidronate with standard induction and maintenance chemotherapy in patients with newly diagnosed high-grade osteosarcoma.
2. Determine the frequency of favorable tumor necrosis produced in patients treated with this regimen.
3. Determine the event-free survival of patients without metastatic disease at presentation treated with this regimen.
4. Determine the prosthesis failure-free survival of patients treated with this regimen and who ultimately undergo limb preservation surgery with insertion of an endoprosthesis.

Entry Criteria

Disease Characteristics:

• Histologically confirmed high-grade osteosarcoma
  • Newly diagnosed
  • Previously untreated
    • Prior definitive surgical resection of primary tumor allowed



• No history of Paget's disease

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy

Surgery

• See Disease Characteristics

Other

• No prior treatment for cancer
• No concurrent enrollment on another therapeutic study

Patient Characteristics:

Age

• Any age

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Platelet count at least 100,000/mm³
• Absolute neutrophil at least 1,000/mm³

Hepatic

• AST no greater than 3 times upper limit of normal (ULN)
• Bilirubin no greater than 1.5 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Cardiovascular

• Shortening fraction at least 28% by echocardiogram

  OR

• Ejection fraction at least 50% by radionuclide angiogram
• No history of pericarditis or myocarditis
• No history of symptomatic arrhythmia
• No history of symptomatic cardiac conduction abnormalities

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of other cancer

Expected Enrollment

A total of 75 patients (50 with localized disease; 25 with metastatic disease) will be accrued for this study within 3-4 years.

Outcomes

Event-free survival 3 years after completion of study treatment
Prosthesis survival as assessed by prosthesis failure when surgery is required

Safety and toxicity as assessed by creatinine and creatinine clearance monthly prior to each course and for 1 year after completion of study treatment
Tumor necrosis as assessed by the Huvos grading system 12 weeks after beginning treatment, at time of definitive surgery after induction chemotherapy
Radiographic response as assessed by RECIST criteria 10 weeks after beginning treatment, after induction chemotherapy, and before definitive surgery
Correlate biological studies with clinical outcome as assessed by protocol 97-094 "Chemotherapy Resistance in Osteogenic Sarcoma) at diagnosis

Outline

Patients are stratified according to extent of disease (localized vs metastatic).

• Induction therapy: Patients receive standard chemotherapy comprising cisplatin IV over 4 hours and doxorubicin IV over 15-30 minutes on weeks 0 and 5 and high-dose methotrexate IV over 4 hours on weeks 3, 4, 8, and 9. Patients also receive pamidronate IV over 2-4 hours beginning approximately 3 days after initiation of chemotherapy on week 0 and repeating once every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

• Surgery*: Patients undergo surgical resection of primary tumor on week 10 and then proceed to maintenance therapy. Patients with metastatic disease undergo further surgery of metastatic sites after recovery from definitive resection of the primary tumor before proceeding to maintenance therapy.

 [Note: *Patients who have undergone definitive surgical resection before study entry may proceed to maintenance therapy or, if appropriate, surgical resection of metastatic disease]

• Maintenance therapy: Patients receive standard chemotherapy comprising cisplatin IV over 4 hours on weeks 0 and 5; doxorubicin IV over 15-30 minutes on weeks 0, 5, 10, and 15; and high-dose methotrexate IV over 4 hours on weeks 3, 4, 8, 9, 13, 14, 18, and 19. Patients also receive pamidronate as in induction therapy for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed monthly for 1 year.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Paul Meyers, MD, Principal investigator		Ph: 212-639-5952; 800-525-2225 Email: meyersp@mskcc.org

Registry Information
Official Title		A Phase II Study of Chemotherapy and Pamidronate for the Treatment of Newly Diagnosed Osteosarcoma
Trial Start Date		2003-07-08
Registered in ClinicalTrials.gov		NCT00072306
Date Submitted to PDQ		2003-09-30
Information Last Verified		2007-04-29
NCI Grant/Contract Number		CA08748

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