A Phase I Study of OncoLAR® (Registered Trademark) (NSC 685403) With/Without Tamoxifen in Patients With Osteosarcoma

Inclusion Criteria

Must have been diagnosed with osteosarcoma by the age of 25 years.

Patient must have a biopsy proven osteosarcoma and either: a) active tumor with no
available standard therapy options; b) metastatic osteosarcoma at diagnosis, has completed
therapy and has no evidence of active disease; or, c) is status-post any surgery for
recurrent osteosarcoma, either local or metastatic recurrence, and is free of disease by
CT scan.

Measurable disease not required.

Patients with serum creatinine <e; 2.0 mg/dL or creatinine clearance >e; 40 ml/min per
1.73m(2) (if serum creatinine is >e; 2.0 mg/dL).

Patients with normal thyroid function.

Patients with total bilirubin, SGOT and SGPT < twice the upper limit of normal.

Patients with normal direct bilirubin only if total direct bilirubin is abnormal.

Patients with bone marrow criteria: ANC>1500/mm(3) and platelet count >100,000/mm(3).

Patients without a history of insulin-dependent diabetes mellitus or current insulin
requirement. Fasting morning blood glucose <150 mg/dL.

Patients with ECOG performance status of 0, 1 or 2 and a life expectancy of at least 8
weeks.

Patients not on chemotherapy or radiation therapy within the past 2 weeks and recovered
from the acute side effects of prior anti-neoplastic therapy.

Patients with documented negative HIV serology within the past 6 months.

Post-menarcheal patients must have documented negative urine and serum pregnancy test
(B-HCG); when indicated, patient must be willing to take oral contraceptives or other
appropriate contraceptives to avoid pregnancy during the period of treatment.

Patient, parent or guardian must give informed consent.

No pregnant or lactating women.

No women of child-bearing potential who are unable or unwilling to use appropriate
contraceptives during the period of treatment.

No patients with uncorrected hypothyroidism.

No patients with insulin-dependent diabetes mellitus or fasting blood glucose >e; 150
mg/dL.

No patients with HIV infection.

No patients with a history of thromboembolic events who require prophylaxis for
thromboembolic events with anticoagulants once entry into Cohort III has begun.

Patients with a history of symptomatic gallbladder disease must have had a
cholecystectomy.