• Safety
• Response
• Pharmacokinetics

Phase Ib/IIa study to determine the safety and efficacy of inhaled SLIT Cisplatin administered every other week to patients with Osteosarcoma who have disease that has spread to the lung.

Osteosarcoma, preferentially metastasizes to the lung. The presence of lung metastases has a major impact on the prognosis of patients with osteosarcoma. Upon surgical removal of the tumor in the lung, new pulmonary metastases often recur within months suggesting micro-metastatic disease resistant to systemic chemotherapy.

The Sustained release lipid inhalation targeting (SLIT) technology offers the potential ability to attain a prolonged therapeutic effect of cisplatin in the lung by sustained release. The ability to give SLIT Cisplatin by inhalation directly to the lung permits high drug levels at the site of disease with low systemic exposure.

Patients will receive SLIT Cisplatin by inhalation for a 14-day treatment cycle in this phase Ib/IIa, two-center, open-label, study designed to characterize the maximum tolerated dose. Clinical efficacy endpoints will be included and compared to historical controls, in addition to pharmacokinetics characterization. Efficacy will be evaluated after at least 2 cycles of therapy. Safety data, including laboratory parameters and adverse events will be collected to determine the qualitative and quantitative toxicity, and reversibility of toxicity, of SLIT Cisplatin. Pulmonary function tests will be performed at baseline, prior to each course and at off-study.

Inclusion Criteria:

• Histologically proven, Progressive or recurrent high grade osteosarcoma metastatic to the lung
• Measureable pulmonary metastases.
• Less than grade 3 neuropathies, insignificant decreases in cardiac or auditory function
• ECOG performance status of 0, 1 or 2
• FEV1 of 50% or greater of predicted value
• FEV1/FVC ratio of 65% or greater
• Serum creatinine of </= 1.5 mg/dl
• Total bilirubin </= 1.5mg/dl and SGOT or SGPT < 2.5 x upper normal limit
• ANC of >/= 1,000/mm3 and platelet count of >= 100,000/mm3

Exclusion Criteria:

• Grade 3 or higher neuropathy
• Concurrent systemic chemotherapy
• Pulmonary atelectasis
• Significant reactive airway disease
• Concurrent serious infections
• Unstable or serious concurrent medical condition
• Recent major surgery
• Significant pulmonary fibrosis
• Major ventilatory distribution abnormalities
• Osteosarcoma secondary to radiation or premalignant conditions
• History of prior malignancy
• Low grade osteosarcoma, parosteal or periosteal sarcoma