NSCLC Stage IVDONUMNCT03385980
Donation of Post Mortem Tumor Tissues
An observational study of NSCLC Stage IV and CRC, run by Niguarda Hospital at 1 site in Italy.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- NSCLC Stage IV, CRC, CUP
- What is being tested?
- Proteomic analysis
- How many people
- 20 participants
- Where
- 1 siteItaly
- Study dates
- 11 Feb 2016to 30 Apr 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Adult patients with confirmed metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), CUP (cancer of unknown origin syndrome)
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- NSCLC Stage IV, CRC, CUP
- Being tested
- Proteomic analysis
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proteomic analysisOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Post-mortem patients | Post-mortem oncological patients (within 2-6 hrs from death, maximum time for tissue preservation). Receives: Other: Proteomic analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: within 2-6 hours post-mortem
Secondary outcomes (2)
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
Measured: 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
Measured: within 2-6 hours post-mortem
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2017
- Study start11 Feb 2016
- Primary completion30 Dec 2021
- Study completion30 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NSCLC Stage IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Turin, Italy, Fondazione del Piemonte per l'Oncologia
- Responsible party
- Sponsor
- Investigators
- Salvatore Siena, MD, Principal investigator, Niguarda Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03385980
- Sponsor's protocol ID
- 90/317/16
- Acronym
- DONUM
- Status last verified
- Mar 2023
- First submitted
- 15 Dec 2017
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 29990497
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donation of Post Mortem Tumor Tissues to Unravel Cancer Heterogeneity
- ClinicalTrials.gov ID
- NCT03385980
- Acronym / sponsor ID
- DONUM / 90/317/16
- Conditions
- NSCLC Stage IV, CRC, CUP
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Collaborators
- University of Turin, Italy, Fondazione del Piemonte per l'Oncologia
- Study start
- 11 Feb 2016 (actual)
- Primary completion
- 30 Dec 2021 (actual)
- Study completion
- 30 Apr 2022 (actual)
- First posted
- 29 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Post-mortem patients | – | Other: Proteomic analysisPost-mortem oncological patients (within 2-6 hrs from death, maximum time for tissue preservation). |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Adult patients with confirmed metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), CUP (cancer of unknown origin syndrome)
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (2 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Proteomic analysisProteomic 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. | Other | Post-mortem patients |
Primary outcome
Intratumor heterogeneity
Time frame: within 2-6 hours post-mortem
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
2 secondary outcomes
Potential impact on subsequent lines of therapy
Time frame: within 2-6 hours post-mortem
Circulating free tumor DNA
Time frame: within 2-6 hours post-mortem
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
- Background: PubMed 29990497Siravegna 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Salvatore Siena, MD principal investigator
Niguarda Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of NSCLC Stage IV and CRC, run by Niguarda Hospital at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intratumor heterogeneity (time frame: within 2-6 hours post-mortem). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03385980, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2023.