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

Primary Purpose

Osteosarcoma Metastatic, Ewing's Sarcoma Metastatic

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Chemotherapy (gemcitabine & docetaxel) plus BIO-11006
Sponsored by
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteosarcoma Metastatic focused on measuring bone cancer, sarcoma, lung metastases, pediatric cancers

Eligibility Criteria

5 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Histologic verification of Ewing's sarcoma or osteosarcoma at original diagnosis or at relapse
  2. Recurrence within one year of end of previous therapy
  3. Presence of lung metastases
  4. Osteosarcoma patients must be ineligible for curative surgery
  5. Ability to take inhaled medication by nebulizer and be willing to adhere to the BIO-11006 regimen
  6. 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.
  7. Males of reproductive potential must agree to the use of condoms or other methods to ensure effective contraception with partner
  8. Stated willingness to comply with all study procedures and availability for the duration of the study
  9. Provision of signed and dated informed consent form

Exclusion Criteria:

  1. Previously treated and progressed on gemcitabine and docetaxel
  2. Central Nervous System (CNS) metastases
  3. Contraindication to gemcitabine or docetaxel
  4. Known allergic reactions to components of BIO-11006
  5. Use of medications that are primarily metabolized by cytochrome P450 isoenzymes
  6. Treatment with another investigational drug within 8 weeks of enrollment.
  7. Current pneumonia or idiopathic pulmonary fibrosis
  8. Absolute Neutrophil Count (ANC) < 750 cells/mm3
  9. Platelet count < 75,000 cells/mm3
  10. Hemoglobin <8.0 g/dL
  11. Creatinine clearance (CrCL) < 45 mL/min
  12. Bilirubin > upper limit of normal (ULN) for age
  13. AST and/or ALT >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN
  14. Organ transplant or bone marrow transplant recipient
  15. Pregnancy or lactation
  16. Current smoker or tobacco use within 3 months prior to enrollment
  17. Any febrile illness or other severe illness within 2 weeks of enrollment
  18. Known history of human immunodeficiency virus, hepatitis B, hepatitis C or tuberculosis

Sites / Locations

  • Nicklaus Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Chemotherapy plus BIO-11006

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).

Full Information

First Posted
November 11, 2019
Last Updated
November 8, 2022
Sponsor
Nicklaus Children's Hospital f/k/a Miami Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04183062
Brief Title
BIO-11006 for Osteosarcoma and Ewing's Sarcoma Lung Metastases
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 4, 2019 (Actual)
Primary Completion Date
November 4, 2023 (Anticipated)
Study Completion Date
November 4, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nicklaus Children's Hospital f/k/a Miami Children's Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma Metastatic, Ewing's Sarcoma Metastatic
Keywords
bone cancer, sarcoma, lung metastases, pediatric cancers

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chemotherapy plus BIO-11006
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy (gemcitabine & docetaxel) plus BIO-11006
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety - Treatment-emergent adverse events (TEAEs)
Description
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.
Time Frame
Up to 16 months
Secondary Outcome Measure Information:
Title
Efficacy - Progression Free Survival (PFS)
Description
PFS will be measured from Cycle 1 Day 1 until occurrence of event (such as death, disease progression or end of study).
Time Frame
Up to 16 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Guillermo De Angulo, MD
Organizational Affiliation
Nicklaus Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Nicklaus Children's Hospital
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
8420923
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Results Reference
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Citation
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Results Reference
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Citation
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Results Reference
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PubMed Identifier
28561686
Citation
Grohar PJ, Janeway KA, Mase LD, Schiffman JD. Advances in the Treatment of Pediatric Bone Sarcomas. Am Soc Clin Oncol Educ Book. 2017;37:725-735. doi: 10.1200/EDBK_175378.
Results Reference
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PubMed Identifier
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Citation
Hartwig JH, Thelen M, Rosen A, Janmey PA, Nairn AC, Aderem A. MARCKS is an actin filament crosslinking protein regulated by protein kinase C and calcium-calmodulin. Nature. 1992 Apr 16;356(6370):618-22. doi: 10.1038/356618a0.
Results Reference
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PubMed Identifier
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Citation
Singer M, Martin LD, Vargaftig BB, Park J, Gruber AD, Li Y, Adler KB. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat Med. 2004 Feb;10(2):193-6. doi: 10.1038/nm983. Epub 2004 Jan 11.
Results Reference
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BIO-11006 for Osteosarcoma and Ewing's Sarcoma Lung Metastases

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