Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma

Conditions
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Pulmonary Relapse of Osteosarcoma

Intervention / Treatment
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* Drug: Inhaled Lipid Cisplatin (ILC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). 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. Age ≥13 years. Patients must have recovered sufficiently from all acute adverse effects of prior therapies, excluding alopecia. Patients must have an ECOG performance status of 0-2. (Lansky score of 50-100 if < 16 years old). 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). Patients must have adequate renal function as defined by a serum creatinine of ≤ 1.5 mg/dl. 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. 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. Signed informed consent including, where applicable, the consent of the patient's legal guardian. Exclusion Criteria: Current extrapulmonary disease. Current macroscopic pulmonary lesions. Greater than 2 pulmonary recurrences. Greater than 4 weeks since thoracotomy rendering patient free of macroscopic disease. Females who are pregnant or breast-feeding. 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. Contraindication to or unwillingness to undergo multiple CT scans and chest X-rays. Unwillingness or inability to comply with the study protocol for any other reason. 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

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ILC<br>Inhaled Lipid Cisplatin (ILC) will be administered every two weeks via nebulization and inhalation. | Drug: Inhaled Lipid Cisplatin (ILC)<br>* ILC is provided as cisplatin in a lipid complex suspended in a saline solution. Every two weeks, the patient will receive 36 mg/m2 (measured as concentration of cisplatin) of ILC via nebulization. Treatment may continue for up to 1 year.<br>* Other names: Lipid cisplatin complex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observed Relapse Free Interval (RFI) | Observed relapse free interval (RFI) will be compared to historical controls. Relapse free interval is defined as the time of diagnosis of the previous relapse to time of diagnosis of the new relapse. | At relapse, estimated at 6-12 months average. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median, 1, 2 and 5 year Overall Survival (OS) | The percentage of patients alive at 1, 2 and 5 years and the median overall survival. | 1, 2 and 5 Years | 
| Median, 1, 2 and 5 year Event Free Survival (EFS) | The percentage of patients surviving without disease relapse at 1, 2 and 5 years and the median event free survival. | 1, 2 and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary relapse, Osteosarcoma, Lung metastases, Pediatric osteosarcoma, Inhaled chemotherapy, Inhaled Lipid Cisplatin