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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04622423

Registration number

NCT04622423

Ethics application status

Date submitted

4/11/2020

Date registered

10/11/2020

Titles & IDs

Public title

Advanced Therapies for Liver Metastases

Scientific title

Advanced Immune Gene and Cell Therapies for Liver Metastases

Secondary ID [1]

22737

Secondary ID [2]

LiMeT

Universal Trial Number (UTN)

Trial acronym

LiMeT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Pancreatic Ductal Adenocarcinoma (PDAC)

Colorectal Cancer (CRC)

Liver Metastasis

Condition category

Condition code

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Cancer

Liver

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure

Study type

Observational

Patient registry

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

PDAC liver-MTS - Adult patients with clinical /radiological diagnosis/suspicious of PDAC metastatic to the liver, with subsequent cytological/histological confirmation (stage IV disease, AJCC) from liver resection/metastasectomy or core liver biopsy.

CRC liver-MTS - Adult patients with histologically or cytologically confirmed diagnosis of CRC metastatic to the liver with indication to surgical resection (upfront or after neoadjuvant therapy).

Primary non-MTS PDAC - Adult patients with clinical/radiological diagnosis of primary non-metastatic PDAC, candidates for surgical resection with radical intent of the primary tumor (upfront surgery or after neoadjuvant therapy). These patients will be monitored for early diagnosis of metachronous hepatic PDAC MTS by follow up testing.

Healthy volunteers - Negative control for the clinical study.

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Definition of tumor mutational burden, epigenetic and gene expression profile of the CRC and PDAC metastatic liver at bulk and at single cell level

Timepoint [1]

After liver metastasis/primary tumor resection/biopsy, usually within 12 months

Primary outcome [2]

Characterization of the immune landscapes of CRC and, if possible, PDAC liver MTS by high dimensional flow cytometry

Timepoint [2]

For tissue specimens: immediately after tumor tissue resection/biopsy (analyses on fresh samples); for blood specimens: after blood drawing, usually within 12 months (analyses on fresh and/or thawed samples)

Primary outcome [3]

Histological validation of the molecular results obtained in 1. and 2.

Timepoint [3]

After liver metastasis/primary tumor resection/biopsy, usually within 12 months

Primary outcome [4]

Definition of the antigenic landscape and TCR repertoire of CRC and PDAC liver MTS

Timepoint [4]

After liver metastasis/primary tumor resection/biopsy, usually within 12 months

Secondary outcome [1]

Evaluation of the molecular and cellular composition of CRC and, if possible, PDAC liver MTS by spatial transcriptomics technologies (NICHE-seq and Visium)

Timepoint [1]

After liver metastasis/primary tumor resection/biopsy, usually within 12 months

Secondary outcome [2]

Collection of clinical follow-up data

Timepoint [2]

CRC patients: throughout the postoperative follow-up, for a maximum of 36 months; PDAC patients: throughout the postoperative follow-up, for a maximum of 24 months

Secondary outcome [3]

Collection and biobanking of follow-up samples from patients with CRC and metachronous PDAC MTS to the liver

Timepoint [3]

CRC: during the postoperative follow-up (up to 36 months), at six-month intervals; PDAC: during the postoperative follow-up (up to 24-months), at time of liver recurrence

Secondary outcome [4]

Biobanking of biospecimens collected from CRC and PDAC patients and from healthy donors

Timepoint [4]

Throughout the protocol (7 years)

Eligibility

Key inclusion criteria

Inclusion and exclusion criteria - CRC patients

Inclusion criteria:

1. Patients with histologically or cytologically confirmed diagnosis of CRC metastatic to the liver (stage IV disease, AJCC)
2. Patients with indication to surgical resection and/or chemotherapy treatment
3. Age =18
4. ECOG PS 0-1 at enrollment
5. Written informed consent
6. Patients will be treated in IRCCS San Raffaele

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Yes

Key exclusion criteria

Exclusion criteria:

1. Pregnancy or lactation
2. Inability to provide a written informed consent
3. Extraepatic disease with the exception of selected cases in which the coexistence of extrahepatic disease does not constitute an exclusion criterion for hepatic resective surgery (for example in patients with extraepatic lesions in remission or in any case stabilized by chemotherapy)
4. Severe comorbidities (e.g. cardiac diseases, history of psychiatric disabilities, HIV, autoimmune disorders)
5. Concurrent or previous other malignancy within 5 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy
6. Other conditions (medical or psychiatric) that in the judgment of Investigators would make the patient an inappropriate candidate for the study

Inclusion and exclusion criteria - PDAC patients

Inclusion criteria:

1. Patients with clinical/radiological diagnosis/suspicious of pancreatic adenocarcinoma metastatic to the liver, with subsequent cytological/histological confirmation (stage IV disease, AJCC)
2. Age =18
3. Karnofsky performance status =50
4. Metastatic pancreatic adenocarcinoma patients with histological specimens from whole liver metastasis biopsy or core liver biopsy collected at IRCCS San Raffaele and stored in the institutional biobank Centro Risorse Biologiche (CRB-OSR)
5. Written Informed consent
6. Patients with clinical/radiological diagnosis of not metastatic primary PDAC that will undergo pancreatic resection at IRCCS San Raffaele

Exclusion criteria:

1. Severe comorbidities (e.g., cardiac diseases, history of psychiatric disabilities) representing an absolute contraindication for whole or core liver metastasis biopsy
2. Pregnancy or lactation
3. Inability to provide a written informed consent
4. Metastatic pancreatic adenocarcinoma patients enrolled in other research trials entailing the analysis of the liver metastasis histological sample

Study design

Purpose

Duration

Selection

Timing

Prospective

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Data analysis

Reason for early stopping/withdrawal

Other reasons

Date of first participant enrolment

Anticipated

Actual

6/11/2019

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

30/06/2026

Actual

Sample size

Target

475

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Recruitment outside Australia

Country [1]

Italy

State/province [1]

Milan

Funding & Sponsors

Primary sponsor type

Other

Name

IRCCS San Raffaele

Address

Country

Other collaborator category [1]

Other

Name [1]

Università Vita-Salute San Raffaele

Address [1]

Country [1]

Ethics approval

Ethics application status

Summary

Brief summary

Liver metastases (MTS) are the main cause of death for patients affected by colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC), thus representing the major unmet clinical need for these malignancies.

Based on preliminary and published data, the investigators hypothesize that innovative immune, gene and cell therapy approaches might overcome the tolerogenic liver microenvironment and represent powerful therapeutic tools for liver MTS of PDAC and CRC.

The investigators have therefore planned an observational clinical study to enroll distinct cohorts of patients (i.e., metastatic CRC, metastatic and non-metastatic PDAC) and finely characterize, through integrated state-of-the-art -omics, the immune and non-immune microenvironment of their primary tumor and/or liver metastases as well as correlate changes in the activation status and phenotype of peripheral blood leukocytes. Healthy volunteers will be enrolled as negative controls.

The investigators aim at identifying: i) actionable tumor associated antigens (TAAs) and local immune suppressive and regulatory pathways; ii) biological parameters for early diagnosis of relapse; iii) the effect of therapies on the shaping of anti-tumor immune responses.

Data collected will be instrumental for the generation of novel advanced therapy medicinal products (ATMPs). Indeed, this protocol is part of a multi-partner translational program, supported by the AIRC 5 per Mille 2019 grant, focused on the development, validation and implementation for clinical testing of ATMPs to ameliorate the cure of CRC and PDAC and possibly help the study of other solid tumors.

Moreover, the systematic and long-term follow-up of enrolled patients will possibly point at early predictors of differential prognosis and patients' categories eligible for tailored therapies, including those with the novel ATMPs.

Trial website

https://clinicaltrials.gov/study/NCT04622423

Trial related presentations / publications

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Cortesi F, Delfanti G, Grilli A, Calcinotto A, Gorini F, Pucci F, Luciano R, Grioni M, Recchia A, Benigni F, Briganti A, Salonia A, De Palma M, Bicciato S, Doglioni C, Bellone M, Casorati G, Dellabona P. Bimodal CD40/Fas-Dependent Crosstalk between iNKT Cells and Tumor-Associated Macrophages Impairs Prostate Cancer Progression. Cell Rep. 2018 Mar 13;22(11):3006-3020. doi: 10.1016/j.celrep.2018.02.058.
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Public notes

 This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts

Principal investigator

Name

Chiara Bonini, MD

Address

Vita-Salute San Raffaele University, IRCCS San Raffaele

Country

Phone

Fax

Contact person for public queries

Name

Chiara Bonini, MD

Address

Country

Phone

0226434790

Fax

bonini.chiara@hsr.it

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

Undecided

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol	Study Protocol and Statistical Analysis Plan	https://cdn.clinicaltrials.gov/large-docs/23/NCT04622423/Prot_SAP_002.pdf
Statistical analysis plan	Study Protocol and Statistical Analysis Plan	https://cdn.clinicaltrials.gov/large-docs/23/NCT04622423/Prot_SAP_002.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT04622423

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Did you know?

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04622423