Identification and Characterization of Predictive Factors of Onset of Bone Metastases in Cancer Patients

NCT03895216 | Completed DMC

• 1 other identifier: CE AVEC 352/2018/Sper/IOR
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the present study is to identify deregulated miRNAs in oncological patients with bone metastases present within the circulating exosomes and responsible for the biological mechanisms involved in the process of bone metastasis, in order to obtain a panel of biomarkers predictive of this risk. Through appropriate molecular screening methods a specific panel of significantly deregulated miRNAs will be identified; subsequently bioinformatics analyzes through the use of dedicated databases will be carried out, based on literature data and predicted protein targets in order to identify their potential role in tumor progression, and especially in the onset of bone metastases. Attention, therefore, may be focused on the individual miRNAs identified through individual analysis analyzes of gene expression. These biomarkers could also serve as therapeutic targets, allowing to improve the effectiveness of current therapies and to undertake timely and appropriate therapeutic choices, developed on the basis of the patient's molecular characteristics

Conditions

Bone Metastases

Keywords

MicroRNAs; Bone Metastases; Exosomes

Outcome Measures

Primary Outcomes (2)

• Changes in miRNAs content of circulating tumor exosomes

  Identification of miRNA isolated from circulating tumor exosomes and their changes will be done through expression profiling studies using Next Generation Sequencing (NGS) during follow-up time points. Molecular characterization will be performed on miRNA samples isolated from circulating tumor exosomes separated from the plasma in order to identify new markers related to tumor progression (bone metastases).

  Within 24 hours before surgery, within 48 hours of metastasectomy or bone biopsy, and follow-up checks at 1, 3, 6 months and 1 year

• Change in protein content of circulating tumor exosomes

  Qualitative and quantitative proteomic analysis of the content of circulating tumor exosomes will be performed by using Triple TOF mass spectrophotometer and variation during follow-up time points wil be measured.

  Within 24 hours before surgery, within 48 hours of metastasectomy or bone biopsy, and follow-up checks at 1, 3, 6 months and 1 year

Secondary Outcomes (2)

• Relationship between plasma levels of circulating tumor exosomes and their content in miRNAs with overall survival and progression of the disease.

  Within 24 hours before surgery, within 48 hours of metastasectomy or bone biopsy, and follow-up checks at 1, 3, 6 months and 1 year

• Cross-talk between isolated circulating tumor exosomes and commercial lines of bone tissue cells in the metastatic process.

  Within 24 hours before surgery, within 48 hours of metastasectomy or bone biopsy, and follow-up checks at 1, 3, 6 months and 1 year

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

A maximum number of 25 patients with metastatic bone lesions is expected to be enrolled and who must undergo metastasectomy or who must perform a bone biopsy of the metastasis. Patients will be enrolled in the clinical trial only after providing written informed consent.

You may qualify if:

• Diagnosis of oncological pathology with evidence of disease progression and presence of bone metastases;
• Patients who have to undergo biopsy of bone metastases or clinical metastasectomy. The analysis of the circulated biomarkers is done in all patients who are subjected to biopsy or metastasis resection to be sure of the diagnosis of bone metastasis, and to have the opportunity to follow patients in the follow-up provided by this type of surgical treatment.
• Life expectancy over 6 months;
• Patients able to provide written informed consent to the study.

You may not qualify if:

• Severe cognitive deficits or psychiatric disorders;
• Patients who do not wish or cannot comply with the study protocol;
• Women of childbearing age who are pregnant or breast-feeding. The protocol excludes pregnant patients because, in the case of metastasectomy, the anesthesia associated with this procedure is completely discouraged in pregnant women and, in addition, any factor is to be avoided (such as a different hormonal arrangement linked to pregnancy ) that can jeopardize or introduce a bias in the results.

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead

Study Sites (1)

Dipartimento Rizzoli Sicialia - Istituto Ortopedico Rizzoli

Bagheria, Palermo, 90011, Italy

Location

Related Publications (5)

• Raimondi L, De Luca A, Costa V, Amodio N, Carina V, Bellavia D, Tassone P, Pagani S, Fini M, Alessandro R, Giavaresi G. Circulating biomarkers in osteosarcoma: new translational tools for diagnosis and treatment. Oncotarget. 2017 Aug 3;8(59):100831-100851. doi: 10.18632/oncotarget.19852. eCollection 2017 Nov 21.

  PMID: 29246026 RESULT

• Graveel CR, Calderone HM, Westerhuis JJ, Winn ME, Sempere LF. Critical analysis of the potential for microRNA biomarkers in breast cancer management. Breast Cancer (Dove Med Press). 2015 Feb 23;7:59-79. doi: 10.2147/BCTT.S43799. eCollection 2015.

  PMID: 25759599 RESULT

• Macias M, Alegre E, Diaz-Lagares A, Patino A, Perez-Gracia JL, Sanmamed M, Lopez-Lopez R, Varo N, Gonzalez A. Liquid Biopsy: From Basic Research to Clinical Practice. Adv Clin Chem. 2018;83:73-119. doi: 10.1016/bs.acc.2017.10.003. Epub 2017 Nov 23.

  PMID: 29304904 RESULT

• Kai K, Dittmar RL, Sen S. Secretory microRNAs as biomarkers of cancer. Semin Cell Dev Biol. 2018 Jun;78:22-36. doi: 10.1016/j.semcdb.2017.12.011. Epub 2017 Dec 19.

  PMID: 29258963 RESULT

• Li A, Zhang T, Zheng M, Liu Y, Chen Z. Exosomal proteins as potential markers of tumor diagnosis. J Hematol Oncol. 2017 Dec 27;10(1):175. doi: 10.1186/s13045-017-0542-8.

  PMID: 29282096 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma and circulating exosomes, microRNA

Study Officials

• Gianluca Giavaresi, MD

  Istituto Ortopedico Rizzoli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: March 29, 2019
• Study Start: December 3, 2018
• Primary Completion: May 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 22, 2022

Record last verified: 2022-03

Locations

IT (1)