Donation of Post Mortem Tumor Tissues

NSCLC Stage IV Clinical Trial

— DONUM  

Official title:

Donation of Post Mortem Tumor Tissues to Unravel Cancer Heterogeneity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03385980
• Other study ID #: 90/317/16
• Status: Completed
• Start date: February 11, 2016
• Est. completion date: April 30, 2022

Study information

• Verified date: March 2023
• Source: Niguarda Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

DONUM is an observational prospective independent protocol for patients with advanced lung cancer, colorectal cancer or cancer of unknown primary, willing to donate their tumor tissue samples post mortem for biomedical research purposes. All patients who fulfill the inclusion criteria will be eligible for the study after giving their Informed consent. Informed Consent will be obtained in two steps. During the pre-information step patients will be acquainted with the existence of a post-mortem cancer tissue donation research program governed by the DONUM protocol. If the patients manifest interest to participate into the program (in writing) during the pre-information step, they will proceed to step 2 and undergo the final informed consent process.

Description:

Despite the recent technological advancement in genomic and proteomic, the molecular understanding of clonal evolution in solid tumor patients is hampered by intra tumor heterogeneity (ITH), while remaining essential to the effective treatment of patients. Recent evidence suggests that branched evolutionary tumor growth may contribute to ITH both within a primary tumor and between primary and metastatic tumors. To study the full extent and consequences of ITH, and grasp clonal evolution, the investigators need to have access not only to circulating biomarkers (circulating tumor DNA) but also, simultaneously and separately, to the primary tumor and all its derived metastases. However multiple biopsies in live patients are neither medically feasible, nor ethical acceptable. A lesser known tissue collection method is through rapid tissue donation (RTD), which is the procurement of 'fresh' tissue within 2 hrs following the death of a patient. RTD-based research provides an effective way to investigate advance tumors biology in a manner not possible by any other means. With an RTD approach, the full extent and consequences of tumor heterogeneity can be evaluated by deep sequencing and global analysis of genetic alterations at the protein level of simultaneous core biopsies from several areas of the primary tumor and metastases and correlation with clinical outcome. To investigators' knowledge, no such studies have been done in Italy and are currently being pursued only in selected USA and UK cancer centers.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 30, 2022
• Est. primary completion date: December 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Adult patients with confirmed metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), CUP (cancer of unknown origin syndrome) with life expectancy less than or equal to 3/4 months;

• Age =18;

• Signed informed consent from patient to enter the study and to undergo post-mortem tissue sampling.

Exclusion Criteria:

• Medical, or psychological conditions that would preclude informed consent;

• History of high-risk infections (e.g. HIV-positive, hepatitis C, tuberculosis and Creutzfeldt-Jacob disease).

Related Conditions & MeSH terms

• CRC
• CUP
• NSCLC Stage IV

Intervention

Other:
• Proteomic analysis
Proteomic analysis of tissues collected from all sites of disease, guided by either imaging performed prior to the patient's death or post-mortem findings. Peripheral blood mononuclear cells (PBMC) will be collected with the purpose of identifying somatic changes occurring specifically in the tumor cells and not in normal DNA of the same patient.

Locations

Country	Name	City	State
Italy	ASST GOM Niguarda	Milano

Sponsors (3)

Lead Sponsor	Collaborator
Niguarda Hospital	Fondazione del Piemonte per l'Oncologia, University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (1)

Siravegna G, Lazzari L, Crisafulli G, Sartore-Bianchi A, Mussolin B, Cassingena A, Martino C, Lanman RB, Nagy RJ, Fairclough S, Rospo G, Corti G, Bartolini A, Arcella P, Montone M, Lodi F, Lorenzato A, Vanzati A, Valtorta E, Cappello G, Bertotti A, Lonardi S, Zagonel V, Leone F, Russo M, Balsamo A, Truini M, Di Nicolantonio F, Amatu A, Bonazzina E, Ghezzi S, Regge D, Vanzulli A, Trusolino L, Siena S, Marsoni S, Bardelli A. Radiologic and Genomic Evolution of Individual Metastases during HER2 Blockade in Colorectal Cancer. Cancer Cell. 2018 Jul 9;34(1):148-162.e7. doi: 10.1016/j.ccell.2018.06.004. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intratumor heterogeneity	Procure primary and metastatic tissue of selected solid tumor patients shortly after death in order to investigate ITH (intratumor heterogeneity), using integrated genomic and proteomic analysis	within 2-6 hours post-mortem
Secondary	Potential impact on subsequent lines of therapy	Study ITH as a results of anticancer drugs exposure in order to forecast its potential impact on subsequent lines of therapy	within 2-6 hours post-mortem
Secondary	Circulating free tumor DNA	Study how the genomic landscape provided by the determination of the circulating free tumor DNA (ctDNA) compare to the genomic landscape from all tumor tissues, considered as gold standard	within 2-6 hours post-mortem