Donation of Post Mortem Tumor Tissues (DONUM)

Donation of Post Mortem Tumor Tissues to Unravel Cancer Heterogeneity

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.

Study Overview

• Status: Completed
• Conditions: NSCLC Stage IV; CRC; CUP
• Intervention / Treatment: Other: Proteomic analysis

Detailed 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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Italy
  • Milano, Italy, 20162
    • ASST GOM Niguarda

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with confirmed metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), CUP (cancer of unknown origin syndrome)

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Post-mortem patients; Post-mortem oncological patients (within 2-6 hrs from death, maximum time for tissue preservation).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Niguarda Hospital
• Collaborators: University of Turin, Italy; Fondazione del Piemonte per l'Oncologia
• Investigators: Principal Investigator: Salvatore Siena, MD, Niguarda Cancer Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2016
• Primary Completion (Actual): December 30, 2021
• Study Completion (Actual): April 30, 2022

Study Registration Dates

• First Submitted: December 15, 2017
• First Submitted That Met QC Criteria: December 20, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 90/317/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No