Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma

Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma

To establish whether treatment with Inhaled Lipid Cisplatin (ILC) is effective in delaying/preventing pulmonary relapse in osteosarcoma patients in complete surgical remission following one or two prior pulmonary relapses.

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