免费获得国外相关药品，最快 1 个工作日回馈药物信息
出境医 / 临床实验 / Donation of Post Mortem Tumor Tissues (DONUM)
Donation of Post Mortem Tumor Tissues (DONUM)
Study Description
Brief 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.
| Condition or disease | Intervention/treatment |
|---|---|
| NSCLC Stage IV CRC CUP | 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 Design
| Study Type : | Observational |
| Estimated Enrollment : | 20 participants |
| Observational Model: | Other |
| Time Perspective: | Prospective |
| Official Title: | Donation of Post Mortem Tumor Tissues to Unravel Cancer Heterogeneity |
| Actual Study Start Date : | February 11, 2016 |
| Estimated Primary Completion Date : | December 30, 2020 |
| Estimated Study Completion Date : | April 30, 2021 |
Arms 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.
|
Outcome Measures
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- Potential impact on subsequent lines of therapy [ Time Frame: within 2-6 hours post-mortem ]Study ITH as a results of anticancer drugs exposure in order to forecast its potential impact on subsequent lines of therapy
- Circulating free tumor DNA [ Time Frame: within 2-6 hours post-mortem ]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
Biospecimen Retention: Samples With DNA
Primary and metastatic tissues and peripheal blood samples
Eligibility Criteria
| Ages Eligible for Study: | Child, Adult, Older Adult |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| 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)
Criteria
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).
Contacts and Locations
Contacts
| Contact: Salvatore Siena, MD | +39026444 ext 2291 | salvatore.siena@ospedaleniguarda.it | |
| Contact: Silvia Ghezzi, Biologist | +39026444 ext 3695 | silvia.ghezzi@ospedaleniguarda.it |
Locations
| Italy | |
| ASST GOM Niguarda | Recruiting |
| Milano, Italy, 20162 | |
| Contact: Salvatore Siena, MD +39026444 ext 2291 salvatore.siena@ospedaleniguarda.it | |
| Contact: Silvia ghezzi, Biologist +39026444 ext 3695 silvia.ghezzi@ospedaleniguarda.it | |
Sponsors and Collaborators
Niguarda Hospital
University of Turin, Italy
Fondazione del Piemonte per l'Oncologia
Investigators
| Principal Investigator: | Salvatore Siena, MD | Niguarda Cancer Center |
| Tracking Information | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| First Submitted Date | December 15, 2017 | ||||||||
| First Posted Date | December 29, 2017 | ||||||||
| Last Update Posted Date | April 24, 2020 | ||||||||
| Actual Study Start Date | February 11, 2016 | ||||||||
| Estimated Primary Completion Date | December 30, 2020 (Final data collection date for primary outcome measure) | ||||||||
| Current Primary Outcome Measures |
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
|
||||||||
| Original Primary Outcome Measures | Same as current | ||||||||
| Change History | |||||||||
| Current Secondary Outcome Measures |
|
||||||||
| Original Secondary Outcome Measures | Same as current | ||||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
| Descriptive Information | |||||||||
| Brief Title | Donation of Post Mortem Tumor Tissues | ||||||||
| Official Title | Donation of Post Mortem Tumor Tissues to Unravel Cancer Heterogeneity | ||||||||
| Brief 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. | ||||||||
| 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 | ||||||||
| Study Design | Observational Model: Other Time Perspective: Prospective |
||||||||
| Target Follow-Up Duration | Not Provided | ||||||||
| Biospecimen | Retention: Samples With DNA Description:
Primary and metastatic tissues and peripheal blood samples
|
||||||||
| 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) | ||||||||
| Condition |
|
||||||||
| 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.
|
||||||||
| Study Groups/Cohorts | Post-mortem patients
Post-mortem oncological patients (within 2-6 hrs from death, maximum time for tissue preservation).
Intervention: Other: Proteomic analysis
|
||||||||
| 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. | ||||||||
|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
| Recruitment Information | |||||||||
| Recruitment Status | Recruiting | ||||||||
| Estimated Enrollment |
20 | ||||||||
| Original Estimated Enrollment | Same as current | ||||||||
| Estimated Study Completion Date | April 30, 2021 | ||||||||
| Estimated Primary Completion Date | December 30, 2020 (Final data collection date for primary outcome measure) | ||||||||
| Eligibility Criteria |
Inclusion Criteria:
Exclusion Criteria:
|
||||||||
| Sex/Gender |
|
||||||||
| Ages | Child, Adult, Older Adult | ||||||||
| Accepts Healthy Volunteers | No | ||||||||
| Contacts |
|
||||||||
| Listed Location Countries | Italy | ||||||||
| Removed Location Countries | |||||||||
| Administrative Information | |||||||||
| NCT Number | NCT03385980 | ||||||||
| Other Study ID Numbers | 90/317/16 | ||||||||
| Has Data Monitoring Committee | No | ||||||||
| U.S. FDA-regulated Product |
|
||||||||
| IPD Sharing Statement |
|
||||||||
| Responsible Party | Niguarda Hospital | ||||||||
| Study Sponsor | Niguarda Hospital | ||||||||
| Collaborators |
|
||||||||
| Investigators |
|
||||||||
| PRS Account | Niguarda Hospital | ||||||||
| Verification Date | April 2020 | ||||||||
