BIO-11006 for Osteosarcoma and Ewing's Sarcoma Lung Metastases

Study Overview
=================
Brief Summary
-----------------
This is a Phase 2 study of an investigational drug, BIO-11006, for the treatment of lung metastases in pediatric patients with advanced osteosarcoma or Ewing's sarcoma. This study will enroll up to 10 patients aged between 5 and 21 at Nicklaus Children's Hospital in Miami, FL. Patients will receive BIO-11006 in addition to chemotherapy consisting of gemcitabine and docetaxel. This study will test the hypothesis that BIO-11006 will enhance the effect of the gemcitabine and docetaxel chemotherapy to treat lung metastases in osteosarcoma and Ewing's sarcoma.

Detailed Description
-----------------
This is a Phase 2, controlled study of BIO-11006 peptide given in addition to Gemcitabine and Docetaxel (GemTax) in the treatment of patients with advanced osteosarcoma or Ewing's sarcoma with lung metastases. Patients will receive BIO-11006 in addition to GemTax chemotherapy, which is a current institutional treatment option for recurrent Osteosarcoma and Ewings's Sarcoma. The BIO-11006 inhalation solution will be given by mouth inhalation twice daily. BIO-11006 will be given during the first three cycles and then will be stopped. Patients will continue on GemTax for up to 6 additional cycles and will be clinically assessed before every cycle and have standard-of-care imaging assessments after cycle 3, 6 and 9. If the patient shows lung progression (either clinical or on imaging) at any point after cycle 4 has been given, but had shown at least a partial response during the tumor assessment after cycle 3, BIO-11006 may be re-started at the discretion of the investigator and continued for the duration of the GemTax treatment. Subjects will be followed for disease status during routine clinical follow-ups for 9 months post the end of study treatment. The trial will be conducted at a single site.

Official Title
-----------------
A Phase 2 Study of the Safety and Efficacy of BIO-11006 in the Treatment of Recurrent Osteosarcoma and Ewing's Sarcoma in Patients With Lung Metastases

Conditions
-----------------
Osteosarcoma Metastatic, Ewing's Sarcoma Metastatic

Intervention / Treatment
-----------------
* Drug: Chemotherapy (gemcitabine & docetaxel) plus BIO-11006


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic verification of Ewing's sarcoma or osteosarcoma at original diagnosis or at relapse Recurrence within one year of end of previous therapy Presence of lung metastases Osteosarcoma patients must be ineligible for curative surgery Ability to take inhaled medication by nebulizer and be willing to adhere to the BIO-11006 regimen Females of reproductive potential must have a negative pregnancy test at screening and must agree to use a method of highly effective contraception during study participation. Males of reproductive potential must agree to the use of condoms or other methods to ensure effective contraception with partner Stated willingness to comply with all study procedures and availability for the duration of the study Provision of signed and dated informed consent form Exclusion Criteria: Previously treated and progressed on gemcitabine and docetaxel Central Nervous System (CNS) metastases Contraindication to gemcitabine or docetaxel Known allergic reactions to components of BIO-11006 Use of medications that are primarily metabolized by cytochrome P450 isoenzymes Treatment with another investigational drug within 8 weeks of enrollment. Current pneumonia or idiopathic pulmonary fibrosis Absolute Neutrophil Count (ANC) < 750 cells/mm3 Platelet count < 75,000 cells/mm3 Hemoglobin <8.0 g/dL Creatinine clearance (CrCL) < 45 mL/min Bilirubin > upper limit of normal (ULN) for age AST and/or ALT >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN Organ transplant or bone marrow transplant recipient Pregnancy or lactation Current smoker or tobacco use within 3 months prior to enrollment Any febrile illness or other severe illness within 2 weeks of enrollment Known history of human immunodeficiency virus, hepatitis B, hepatitis C or tuberculosis

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 21 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chemotherapy plus BIO-11006<br>Patients will receive BIO-11006 in addition to GemTax chemotherapy. The BIO-11006 inhalation solution will be given by mouth inhalation twice daily. BIO-11006 will be given during the first three cycles of GemTax and then will be stopped. Subjects will continue with GemTax treatment for three additional cycles. If the patient shows lung progression (either clinical or on imaging) at any point after cycle 4 has been given, but had shown at least a partial response during the tumor assessment after cycle 3, BIO-11006 may be re-started at the discretion of the investigator and continued for the duration of the GemTax treatment. | Drug: Chemotherapy (gemcitabine & docetaxel) plus BIO-11006<br>* BIO-11006 will be administered at a dose of 75 mg twice daily for patients over 5 years of age and under 18 years of age or 125 mg twice daily for patients 18 years of age or older. The study drug will be administered twice daily by nebulizer over 20 minutes. GemTax will be administered in 21-day cycles. Gemcitabine will be administered at a dose of 900 mg/m2 IV over 90 minutes on days 1 and 8. Docetaxel will be administered at a dose of 75 mg/m2 IV over 60 minutes on day 8.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety - Treatment-emergent adverse events (TEAEs) | Frequency, type, severity, and duration of TEAEs. Sources of TEAEs may include spontaneous patient reports, results of physical examinations, and clinical laboratory measurements. Simple descriptive statistics of frequencies, centrality and variability will be utilized to tabulate and summarize TEAEs. If sufficient number of TEAEs will be captured, frequencies, duration and severity will be compared. | Up to 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Progression Free Survival (PFS) | PFS will be measured from Cycle 1 Day 1 until occurrence of event (such as death, disease progression or end of study). | Up to 16 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
bone cancer, sarcoma, lung metastases, pediatric cancers