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Inhibition of SENP1 for the Suppression of OS Growth and Metastasis

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ClinicalTrials.gov Identifier: NCT03798587
Recruitment Status : Not yet recruiting
First Posted : January 10, 2019
Last Update Posted : January 10, 2019
Sponsor:
Information provided by (Responsible Party):
Istituto Ortopedico Galeazzi

Brief Summary:

The aim of this project is to test a new powerful PNA-based SENP1 inhibitor, previously characterized in an in vitro model of OS cell lines.

The most effective PNA, conjugated with a cell-permeable CPP, which is able to inhibit OS cells viability and invasiveness in both normoxia and hypoxia through SENP1-mediated inhibition of HIF1α, ZEB1, and Akt, will be investigated for its ability to penetrate and silence SENP1 expression in ex vivo human OS tissues.

Primary aim:

To determine the ability of PNA-CPP to penetrate into an ex vivo tridimensional tissue of OS, derived from wasted biological material obtained during OS eradication surgery, and to exert its biological function of inhibiting SENP1 within the tissue.


Condition or disease
Primary Osteosarcoma of Bone

  Show Detailed Description

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 15 participants
Observational Model: Cohort
Time Perspective: Other
Target Follow-Up Duration: 1 Day
Official Title: PNA-mediated Inhibition of the SENP1 Molecular Hub as a Potential Therapeutic Approach for the Suppression of Osteosarcoma Growth and Metastasis (PNA-OS)
Estimated Study Start Date : January 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Group/Cohort
OS patients

Patients with age ≥18 years that were/can be recruited within the IRCCS Istituto Ortopedico Galeazzi BioBanca (ethical committee approval n. 29/INT/2017).

Patients with age <18 years: will be additionally recruited besides the IRCCS Istituto Ortopedico Galeazzi BioBanca.

The target group corresponds to patients hospitalized at Istituto Ortopedico Galeazzi, undergoing surgical eradication of primary osteosarcoma.

Patients will be considered eligible for enrollment in the study if able to sign the consent to the procedure after appropriate information from the reference surgeon or signed by parents or legal guardian after appropriate information from the reference surgeon (if age <18).

Inclusion Criteria:

  • Indication for primary OS eradication surgery
  • Patients hospitalized in Istituto Ortopedico Galeazzi

Exclusion criteria:

-Patients not able to sign the Informed Consent.




Primary Outcome Measures :
  1. Determination of SENP1 expression in OS samples [ Time Frame: 8 months ]
    OS samples, already existing in the BioBanca as frozen samples preserved in liquid nitrogen at BioRep Service-Provider (BioRep S.r.l. Via Olgettina 60, 20132, Milano), will be used to determine the initial expression levels of SENP1 in OS by RT-qPCR. For this, samples will be homogenized, total RNA will be extracted and RT-qPCR will be performed assaying for SENP1 expression levels.

  2. Ex vivo analysis of the PNA-R8 silencing ability in osteosarcoma samples. [ Time Frame: 16 months ]
    Freshly collected OS samples will be preserved in physiological solution until usage. The OS samples will be cut in 3 mm3 pieces, placed in a 24-multiwell culture plate, and cultivated ex vivo as organotypic OS cultures in both normoxia and hypoxia-induced microenvironment under orbital rotation. OS cultures will be treated with senpPNA-R8, and SENP1 expression in naïve and PNA-treated samples will be determined by RT-qPCR and immunohistochemistry in paraffin-embedded sections. The ability of the PNA-R8 to penetrate within the hypoxic core of the OS samples will be assessed: after incubation with scrPNA-R8-Fl, sections will be immediately frozen (-80°C), processed and analyzed by immunofluorescence.


Biospecimen Retention:   Samples Without DNA
Wasted biological material derived from osteosarcoma eradication surgery.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

15 patients with primary OS.

Patients with age ≥18 years that were/can be recruited within the IRCCS Istituto Ortopedico Galeazzi BioBanca (ethical committee approval n. 29/INT/2017).

Patients with age <18 years: will be additionally recruited besides the IRCCS Istituto Ortopedico Galeazzi BioBanca.

The target group corresponds to patients hospitalized at Istituto Ortopedico Galeazzi, undergoing surgical eradication of primary osteosarcoma.

Patients with age ≥18 will be considered eligible for enrollment in the study if able to sign the consent to the procedure after appropriate information from the reference surgeon.

Patients with age <18 will be considered eligible for enrollment in the study if able to provide the consent to the procedure (donation of waste material) signed by parents or legal guardian after appropriate information from the reference surgeon.

Criteria

Inclusion Criteria:

  • Indication for primary OS eradication surgery
  • Patients hospitalized in Istituto Ortopedico Galeazzi

Patients with age ≥18 years: were/can be recruited within the IRCCS Istituto Ortopedico Galeazzi BioBanca (ethical committee approval n. 29/INT/2017).

Patients with age <18 years: will be additionally recruited besides the IRCCS Istituto Ortopedico Galeazzi BioBanca.

Exclusion Criteria:

  • Patients not able to sign the Informed Consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03798587


Contacts
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Contact: Marta Sofia Gomarasca, PhD +39 026621 ext 4068 marta.gomarasca@grupposandonato.it
Contact: Elena Cittera, MSc +39 026621 ext 4057 elena.cittera@grupposandonato.it

Locations
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Italy
IRCCS Istituto Ortopedico Galeazzi Recruiting
Milano, Italy, 20161
Contact: Marta Sofia Gomarasca, PhD    0039022261 ext 4068    marta.gomarasca@grupposandonato.it   
Contact: Elena Cittera, MSc    0039022261 ext 4057    elena.cittera@grupposandonato.it   
Sponsors and Collaborators
Istituto Ortopedico Galeazzi

Additional Information:

Publications of Results:

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Responsible Party: Istituto Ortopedico Galeazzi
ClinicalTrials.gov Identifier: NCT03798587     History of Changes
Other Study ID Numbers: PNA-OS
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma