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

2019-04-03 09:44:28 | BioPortfolio


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


MATERIALS AND METHODS: 1) Removal of whole blood from peripheral vein and separation of plasma from enrolled metastatic cancer patients; 2) Isolation of tumor exosomes circulating from the plasma of cancer patients (Kit Invitrogen: Total Exosome Isolation Reagent); 3) Next generation sequencing methods (NGS) will be used to evaluate the expression profiles of miRNAs isolated from circulating tumor exosomes (MiSeq Illumina System); 4) Mass spectrometry methods will be used for the proteome analysis of circulating exosomes isolated from the plasma of cancer patients (Triple TOFF 5600 Plus System AND HPLC analysis of bioactive and biomarker peptides); 5) 3D cultures for the study of cross-talk between circulating tumor exosomes (isolated from the patients' plasma) and bone tissue cells (using commercial cell lines) as part of the metastatic process (Cellec perfusion bioreactor BioteK AG).

Enrollment Procedures: Patients considered eligible will be enrolled in the study, after providing a written informed consent.

Data Collection: Clinical data will be retrieved by patient's source document. A protocol-specific CRF reporting the results of the analyses will be provided. A CRF is required and should be completed for each included subject.

Ethics: The clinical trial protocol and its documents will be sent before initiating the study to the competent Authorities and Ethics Committees of each participating country for its approval. The responsible investigator will ensure that this study is conducted in agreement with either the most updated Declaration of Helsinki and all the international and local laws that apply to clinical trials and to patient protection. The protocol has been written, and the study will be conducted according to the principles of the ICH Harmonized Tripartite Guideline for Good Clinical Practice (ref:

Informed Consent: All patients will be informed, by the investigator, of the aims of the study, the possible risks and benefits that will derive from the study participation. The Investigator must clearly inform that the patient is free to refuse participation in the study and that can withdraw consent at any time and for any reason. They will be informed as to the strict confidentiality of their patient data, but that their medical records may be reviewed for trial purposes by authorized individuals other than their treating physician. The informed consent procedure must conform to the ICH guidelines on Good Clinical Practice. This implies that "the written informed consent form should be signed and personally dated by the patient or by the patient's legally acceptable representative".

The Investigator must also sign the Informed Consent form, and will keep the original at the site and a copy of the original must be handed to the patient.

The competent ethics committee for each Institution participating to the study must validate local informed consent documents before the study can be opened. It will be emphasized that the participation is voluntary and that the patient is allowed to refuse further participation in the study whenever he/she wants. This will not prejudice the patient's subsequent care.

General Principles for Human Biological Material (HBM) collection: Human biological material (HBM) collection involves the collection and storage of biological material, residual biological material or derivatives in compliance with ethical and technical requirements. Biological material (blood samples) will be centralized and stored at Istituto Ortopedico Rizzoli - Dipartimento Rizzoli-Sicilia, Bagheria (Palermo). From here, the biological material will be used and stored according with the sample characteristic and applicable regulation.

Plasma and circulating exosomes obtained from blood will be stored inside sterile containers (falcon, tubes, eppendorf) in a freezer at the temperature of -80 °C at the Istituto Ortopedico Rizzoli -Dipartimento Rizzoli Sicilia.

The following principles apply to storage of HBM: (a) The Istituto Ortopedico Rizzoli will have a designated person responsible for collection and will act as a communication point; (b) The collected HBM should be documented, i.e. the amount remaining and its location. act as a communication point; and (c) The storage and use of biological material will take place in accordance with the standards of good laboratory practice (GLP) and applicable legislation.

Confidentiality: In order to ensure confidentiality of clinical trial data as disposed the national and European applicable regulation, data will be only accessible for the trial Sponsor and its designees, for monitoring/auditing procedures, the Investigator and collaborators, the Ethics Committee of each corresponding site and the Health Authority. Investigator and the Institution will allow access to data and source documentation for monitoring, auditing, Ethic Committee revision and inspections of Health Authority, but maintaining at all times subject personal data confidentiality as specified in the applicable regulation.

The Investigator must guarantee that patient anonymity is kept at all times and their identity must be protected from unauthorized persons and institutions.

All patients included in the study will be identified with a numeric code, so that no identifiable personal data will be collected. The Investigator must have and conserve a patients' inclusion registry where it figures the personal data of the patient: name, surname, address and corresponding identification code into the study, this register will be kept on the Investigator File.

Publication policy and data ownership: The principal investigator of the study is responsible for the final report, of the publication publish all the data collected as described in the protocol and will ensure that the data are reported responsibly and consistently. In particular, the publication of data deriving from the present study will take place independently of the results obtained. The transmission or dissemination of data, through scientific publications and / or presentation at conferences, congresses and seminars, will take place exclusively following the purely statistical processing of the same, or in an absolutely anonymous form. All the study data are owned by the sponsor.

Study Design


Bone Metastases


Dipartimento Rizzoli Sicialia - Istituto Ortopedico Rizzoli




Istituto Ortopedico Rizzoli

Results (where available)

View Results


Published on BioPortfolio: 2019-04-03T09:44:28-0400

Clinical Trials [1809 Associated Clinical Trials listed on BioPortfolio]

Exercise Prescription in Patients With Bone Metastases

Cancer which has spread to the bone, causing bone metastases (bone tumours) can weaken bone health and increase risk of fractures (breaks). Consequently, patients can be unsure whether to ...

Is Bone Scintigraphy Necessary in cT1N0M0 Pure GGO Non-Small Cell Lung Cancer?

Skeletal is a common metastatic site in patients with non-small cell lung cancer. The incidence of bone metastases is about 20-30% in NSCLC patients. According to the NCCN guidelines, ea...

A Trial of Hypofractionated Radiotherapy (16/2) for the Palliation of Complicated Bone Metastases in Patients With Poor Performance Status

In summary, literature has shown that hypofractionated radiotherapy regimens are efficacious in patients with complicated bone metastases and have a low potential for severe treatment-rela...

Short Course Radiation Therapy in Palliative Treatment of Complicated Bone Metastases

Aim of the study is to assess efficacy of a short course radiation treatment in patients with complicated bone metastases

2-[F-18] Fluoro-2-deoxy-D-glucose (FDG) Positron Emission Tomography (PET/CT) and Technetium 99m-methylene Diphosphonate (99m Tc-MDP) Bone Scan in Bone Metastases

The aim of this study is to assess the diagnostic accuracy of 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in comparison to 99mTc-MDP bone scan wit...

PubMed Articles [4413 Associated PubMed Articles listed on BioPortfolio]

Differentiated treatment strategies for bone metastases of the extremities.

Bone metastases are the most common malignant bone tumours and most commonly occur in the spine, pelvis, proximal femur and proximal humerus. Prostate and breast cancer most often metastasize to the b...

Osteoclasts and tumor cells dual targeting nanoparticle to treat bone metastases of lung cancer.

Bone is one of the prone metastatic sites of lung cancer. Osteoclast plays an important role in bone resorption and the growth of bone metastases of lung cancer. In order to treat bone metastases of l...

De-escalation of bone-modifying agents in patients with bone metastases from breast cancer: a systematic review and meta-analysis.

Bone-modifying agents (BMAs) such as bisphosphonates and denosumab are usually administered every 4 weeks (standard) in patients with bone metastases from breast cancer to prevent skeletal-related ev...

Incidence of osteonecrosis of the jaw by the use of osteoclast inhibitors in patients with bone metastases: a retrospective cohort study.

The use of osteoclast inhibitors in metastatic bone disease, increase bone mineral density and reduce the risk of fracture, patients with osteonecrosis have been reported after the chronic use of thes...

Recommendations for single faction radiation therapy and stereotactic body radiation therapy in palliative treatment of bone metastases: A statewide practice patterns survey.

Single fraction (SF) radiotherapy is effective and convenient for patients with painful non-complex bone metastases. Prior survey results reported low recommendation of SF radiotherapy in the US. We s...

Medical and Biotech [MESH] Definitions


Irradiation of one half or both halves of the body in the treatment of disseminated cancer or widespread metastases. It is used to treat diffuse metastases in one session as opposed to multiple fields over an extended period. The more frequent treatment modalities are upper hemibody irradiation (UHBI) or lower hemibody irradiation (LHBI). Less common is mid-body irradiation (MBI). In the treatment of both halves of the body sequentially, hemibody irradiation permits radiotherapy of the whole body with larger doses of radiation than could be accomplished with WHOLE-BODY IRRADIATION. It is sometimes called "systemic" hemibody irradiation with reference to its use in widespread cancer or metastases. (P. Rubin et al. Cancer, Vol 55, p2210, 1985)


A type of osseous tissue which makes up the inner part of bone. It has a spongy, honeycomb-like structure with struts or trabecula and contains the BONE MARROW. It has higher rate of BONE REMODELING turnover than CORTICAL BONE.

Removal of mineral constituents or salts from bone or bone tissue. Demineralization is used as a method of studying bone strength and bone chemistry.

More From BioPortfolio on "Identification and Characterization of Predictive Factors of Onset of Bone Metastases in Cancer Patients"

Quick Search

Relevant Topics

Osteoporosis is a disease in which the bones become extremely porous, are subject to fracture, and heal slowly, occurring especially in women following menopause and often leading to curvature of the spine from vertebral collapse. Follow and track&n...

Biological Therapy
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...

Searches Linking to this Trial