Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma

• Sponsor: Eleison Pharmaceuticals LLC.
• Information provided by (Responsible Party): Eleison Pharmaceuticals LLC.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Relapse of Osteosarcoma	Drug: Inhaled Lipid Cisplatin (ILC)	Phase 2

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	50 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Phase 2 Study of Inhaled Lipid Cisplatin in Pulmonary Recurrent Osteosarcoma
Study Start Date :	August 2012
Estimated Primary Completion Date :	December 2018
Estimated Study Completion Date :	December 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: ILC; Inhaled Lipid Cisplatin (ILC) will be administered every two weeks via nebulization and inhalation.	Drug: Inhaled Lipid Cisplatin (ILC); 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.; Other Names: Cisplatin; Lipid cisplatin complex

Outcome Measures

Primary Outcome Measures :

1. Observed Relapse Free Interval (RFI) [ Time Frame: At relapse, estimated at 6-12 months average. ]
   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.

Secondary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	13 Years and older (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Locations

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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Stanford University Medical Center
Palo Alto, California, United States, 94304
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
The Children's Hospital at Montefiore
Bronx, New York, United States, 10467
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Baylor College of Medicine/Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105

Sponsors and Collaborators

Eleison Pharmaceuticals LLC.

Investigators

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Principal Investigator:	Richard Gorlick, MD	The Children's Hospital at Montefiore
Study Director:	Forrest H Anthony, MD, PhD	Eleison Pharmaceuticals

More Information

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Responsible Party:	Eleison Pharmaceuticals LLC.
ClinicalTrials.gov Identifier:	NCT01650090 History of Changes
Other Study ID Numbers:	EP-ILC-201
First Posted:	July 26, 2012
Last Update Posted:	February 7, 2018
Last Verified:	February 2018

Keywords provided by Eleison Pharmaceuticals LLC.:

Pulmonary relapse; Osteosarcoma; Lung metastases	Pediatric osteosarcoma; Inhaled chemotherapy; Inhaled Lipid Cisplatin

Additional relevant MeSH terms:

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Recurrence; Osteosarcoma; Disease Attributes; Pathologic Processes; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue	Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Cisplatin; Antineoplastic Agents