Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma

ILC is a novel formulation of cisplatin, designed for inhalation by nebulization. The
anticipated pulmonary benefits of ILC over systemic cisplatin therapy are threefold:

- Increased local cisplatin concentrations

- Sustained release of cisplatin in the lungs

- Minimal systemic exposure to cisplatin

In this study, patients currently in surgical complete remission (CR) following one or two
prior relapses of osteosarcoma involving pulmonary disease will be treated with ILC every two
weeks for up to one year. ILC will be administered via nebulization.

Inclusion Criteria:

1. History of osteosarcoma metastatic to the lung(s). (First or second pulmonary
recurrence(s) removed by surgery, and previous second-line systemic chemotherapy is
allowed).

2. Patients must be macroscopically disease free following pulmonary metastectomy of a
single or multiple lesions. Complete remission surgically (free of macroscopic
disease) is required. Pleural disruption and/or microscopic positive margins are
allowed.

3. Age ≥13 years.

4. Patients must have recovered sufficiently from all acute adverse effects of prior
therapies, excluding alopecia.

5. Patients must have an ECOG performance status of 0-2. (Lansky score of 50-100 if < 16
years old).

6. Patients must have recovered sufficiently from surgery and have adequate airflow and
pulmonary reserve. This decision should be at the investigator's discretion taking
into consideration pre-surgery pulmonary function. (As a guideline: adequate airflow
defined by a measured Forced Expiratory Volume (FEV1) not less than 50% of the
predicted value and adequate pulmonary reserve as evidenced by a FEV1/FVC ratio of 65%
or greater).

7. Patients must have adequate renal function as defined by a serum creatinine of ≤ 1.5
mg/dl.

8. Patients must have adequate liver function as defined by total bilirubin of ≤ 1.5
mg/dl and ALT or AST < 2.5 times the institution's upper normal limit.

9. Patients must have adequate bone marrow function as defined by an absolute neutrophil
count (ANC) of ≥ 1,000/mm3 and platelet count of ≥ 100,000/mm3.

10. Signed informed consent including, where applicable, the consent of the patient's
legal guardian.

Exclusion Criteria:

1. Current extrapulmonary disease.

2. Current macroscopic pulmonary lesions.

3. Greater than 2 pulmonary recurrences.

4. Greater than 4 weeks since thoracotomy rendering patient free of macroscopic disease.

5. Females who are pregnant or breast-feeding.

6. Concomitant disease or condition that could interfere with the conduct of the study,
or that would, in the opinion of the investigator, pose an unacceptable risk to the
patient in this study.

7. Contraindication to or unwillingness to undergo multiple CT scans and chest X-rays.

8. Unwillingness or inability to comply with the study protocol for any other reason.

9. Participation in an investigational drug or device study or treatment with any
anti-neoplastic agent within 14 days of the first day of dosing on this study