Pancreatic CancerCLEARNCT07794969
Pancreatic Cancer Lifestyle Evolution And Resistance
An observational study of Pancreatic Cancer, run by IRCCS San Raffaele.
Trial summary
Advanced PDAC patients undergo polychemotherapy, yet responses are highly variable. Transcriptome signatures are emerging as key predictors of treatment response. However, PDAC adapts across sites (primary vs. metastases) and evolves under treatment pressure (pre- vs. post-chemotherapy). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreatic Cancer
- What is being tested?
- Endoscopic Ultrasound with FNA/FNB
- Type of treatment
- Surgery or procedure
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- 31 Oct 2026to 31 Oct 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population consists of adult patients (aged ≥18 years) with a clinical and/or radiological suspicion of Pancreatic Ductal Adenocarcinoma (PDAC) who are scheduled to undergo a diagnostic Endoscopic Ultrasound-guided Tissue Acquisition (EUS-TA) as part of their standard clinical pathway. The population will include both men and women, without restrictions on ethnicity. Including a 10% loss to follow-up, the planned cohort is 150 patients, evenly distributed among the three regimens (mFOL, NG or PAXG).
Who may be able to join
- Age = 18 years
- Willing to sign informed consent
- Patient with CT scan or MRI or EUS with a lesion suspect of PDAC at any clinical stage
- Patients considered fit to receive polychemotherapy with either mFOL, NG or PAXG.
- Patients primarily followed at HSR
Who cannot join
- Patients not willing to sign informed consent
- Pregnancy and breastfeeding
- Cytology positive for malignancies other than PDAC
- Patients who have not performed biopsy for safety or technical reasons
- Patients unfit for polychemotherapy
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Laura Apadula, Research Nurse contact
About this study
Official title: Decoding Environmental Drivers of Adaptive Evolution and Chemotherapy Resistance in Advanced Pancreatic Cancer
Advanced PDAC patients undergo polychemotherapy, yet responses are highly variable. Transcriptome signatures are emerging as key predictors of treatment response. However, PDAC adapts across sites (primary vs. metastases) and evolves under treatment pressure (pre- vs. post-chemotherapy). Moreover, common environmental pollutants, like smoking and microplastics, contribute to carcinogenesis, yet their impact on PDAC evolution and treatment response remains unclear.
To fill these gaps, the CLEAR project aims at investigating:
- transcriptome patterns linked to treatment response;
- effects of smoking and microplastic exposure on treatment outcomes;
- PDAC evolution across organ sites and under chemotherapy. These studies will help uncover biomarkers and factors shaping disease progression, hence paving the ground for personalized therapies.
Read the detailed description
This study aims at identifying and validating transcriptome signatures in patients with Pancreatic Ductal Adenocarcinoma (PDAC) through EUS-guided biopsies. The study hypothesis is that specific molecular profiles (e.g., "basal-like" vs. "classical" subtypes) obtained at the time of diagnosis can predict primary resistance or sensitivity to standard-of-care first-line chemotherapy regimens (mFOL, NG, or PAXG). By correlating these signatures with clinical outcomes, the study seeks to provide a rationale for personalized therapeutic strategies in advanced PDAC.
This is a prospective, single-center, interventional study. Patients with a cytological diagnosis of PDAC (confirmed via Rapid On-Site Evaluation - ROSE) during a standard-of-care EUS-TA are enrolled at baseline. A part of the citology sample is employed for research purpose (RNA-seq). Following the procedure, patients receive standard-of-care chemotherapy (mFOL, NG, or PAXG). The intervention consists of an additional biopsy pass performed during EUS at the time of re-staging after chemotherapy, exclusively for research purposes (RNA-seq). All patients undergo standard longitudinal clinical monitoring to assess Progression-Free Survival (PFS) and Overall Survival (OS) for a total period of 30 months or until death.
Primary Objective:
To identify baseline transcriptomic signatures associated with treatment response to mFOL, NG, and PAXG in advanced PDAC patients.
Primary Endpoint:
Response to treatment assessed every 3 months by RECIST 1.1 criteria and defined as Disease Control Rate at 6 months (DCR-6); Progression-Free Survival (PFS) and Overall Survival (OS) during the follow-up period.
Secondary Objectives:
To investigate the longitudinal evolution of PDAC signatures during treatment
Secondary Endpoints:
Comparison of transcriptome signatures between baseline EUS-biopsy and repeated biopsy after 6 months of treatment.
To evaluate the impact of active smoking on transcriptomic subtypes and treatment outcomes via correlation between smoking status and the distribution of classical vs. basal-like subtypes and clinical outcomes.
To compare signatures between primary and metastatic sites throughout the comparison of transcriptomic patterns between primary tumor and metastatic biopsy samples.
- Conditions
- Pancreatic Cancer
- Being tested
- Endoscopic Ultrasound with FNA/FNB
- Keywords
- pancreatic cancer, chemotherapy, response, resistance, trascriptome, smoking
- Medical subject headings
- Pancreatic Neoplasms, Smoking
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Endoscopic Ultrasound with FNA/FNBProcedure or surgery
After identification of the mass lesion, a tumor sample will be acquired with a standard FNA/FNB needle, as the standard procedure requires. The sample will be taken and stored in a Eppendorf Tube of 1.5ml pre-filled with 300μL 1-Thioglycerol/Homogenization solution _Promega® then stored in a 80°C freezer and transferred every 2 weeks to the CRB for subsequent RNA-seq.
| Study group | Role | What they receive |
|---|---|---|
| Patients with pancreatic adenocarcinoma | The study population consists of adult patients (aged ≥18 years) with a clinical and/or radiological suspicion of Pancreatic Ductal Adenocarcinoma (PDAC) who are scheduled to undergo a diagnostic Endoscopic Ultrasound-guided Tissue Acquisition (EUS-TA) as part of their standard clinical pathway. The population will include both men and women, without restrictions on ethnicity. Including a 10% loss to follow-up, the planned cohort is 150 patients, evenly distributed among the three regimens (mFOL, NG or PAXG). Receives: Procedure: Endoscopic Ultrasound with FNA/FNB |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to treatment at 6 months
Response to treatment assessed every 3 months by RECIST 1.1 criteria and defined as Disease Control Rate at 6 months (DCR-6)
Measured: 6 months
Progression-Free Survival (PFS)
Time of disease progression (PFS)
Measured: 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2026
- Study start31 Oct 2026 (estimated)
- Primary completion31 Oct 2029 (estimated)
- Study completion31 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gabriele Capurso, IRCCS San Raffaele
- Investigators
- Laura Apadula, Nurse, Study chair, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07794969
- Sponsor's protocol ID
- RF-2024-12378165 (the CLEAR)
- Other IDs
- RF-2024-12378165
- Acronym
- CLEAR
- Status last verified
- Aug 2026
- First submitted
- 26 Aug 2026
- Last updated
- 31 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: data might be shared upon reasonable requests
Publications
Reni M, Macchini M, Orsi G, Procaccio L, Malleo G, Carconi C, Rapposelli IG, Bencardino K, Scartozzi M, Balzano G, Tamburrino D, Merelli B, Sperti E, Belfiori G, Liscia N, Bozzarelli S, Di Marco M, Tamburini E, Milella M, Lonardi S, Ercolani G, Mazzola M, Palumbo D, Torri V, Falconi M. Preoperative mFOLFIRINOX versus PAXG for stage I-III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 x 2 factorial phase 3 trial. Lancet. 2026 Dec 20;406(10522):2945-2956. doi: 10.1016/S0140-6736(25)01685-X. Epub 2025 Nov 20.
PubMed 41275879Panzeri V, Manni I, Capone A, Naro C, Sacconi A, Di Agostino S, de Latouliere L, Montori A, Pilozzi E, Piaggio G, Capurso G, Sette C. The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma. Mol Oncol. 2021 Feb;15(2):579-595. doi: 10.1002/1878-0261.12847. Epub 2020 Nov 24.
PubMed 33159833Archibugi L, Ruta V, Panzeri V, Redegalli M, Testoni SGG, Petrone MC, Rossi G, Falconi M, Reni M, Doglioni C, Sette C, Arcidiacono PG, Capurso G. RNA Extraction from Endoscopic Ultrasound-Acquired Tissue of Pancreatic Cancer Is Feasible and Allows Investigation of Molecular Features. Cells. 2020 Nov 30;9(12):2561. doi: 10.3390/cells9122561.
PubMed 33266052
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Decoding Environmental Drivers of Adaptive Evolution and Chemotherapy Resistance in Advanced Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT07794969
- Acronym / sponsor ID
- CLEAR / RF-2024-12378165 (the CLEAR)
- Conditions
- Pancreatic Cancer
- Keywords
- pancreatic cancer, chemotherapy, response, resistance, trascriptome, smoking
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 31 Oct 2026 (estimated)
- Primary completion
- 31 Oct 2029 (estimated)
- Study completion
- 31 Oct 2029 (estimated)
- First posted
- 31 Aug 2026 (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.
Advanced PDAC patients undergo polychemotherapy, yet responses are highly variable. Transcriptome signatures are emerging as key predictors of treatment response. However, PDAC adapts across sites (primary vs. metastases) and evolves under treatment pressure (pre- vs. post-chemotherapy). Moreover, common environmental pollutants, like smoking and microplastics, contribute to carcinogenesis, yet their impact on PDAC evolution and treatment response remains unclear.
To fill these gaps, the CLEAR project aims at investigating:
- transcriptome patterns linked to treatment response;
- effects of smoking and microplastic exposure on treatment outcomes;
- PDAC evolution across organ sites and under chemotherapy. These studies will help uncover biomarkers and factors shaping disease progression, hence paving the ground for personalized therapies.
Detailed description
This study aims at identifying and validating transcriptome signatures in patients with Pancreatic Ductal Adenocarcinoma (PDAC) through EUS-guided biopsies. The study hypothesis is that specific molecular profiles (e.g., "basal-like" vs. "classical" subtypes) obtained at the time of diagnosis can predict primary resistance or sensitivity to standard-of-care first-line chemotherapy regimens (mFOL, NG, or PAXG). By correlating these signatures with clinical outcomes, the study seeks to provide a rationale for personalized therapeutic strategies in advanced PDAC.
This is a prospective, single-center, interventional study. Patients with a cytological diagnosis of PDAC (confirmed via Rapid On-Site Evaluation - ROSE) during a standard-of-care EUS-TA are enrolled at baseline. A part of the citology sample is employed for research purpose (RNA-seq). Following the procedure, patients receive standard-of-care chemotherapy (mFOL, NG, or PAXG). The intervention consists of an additional biopsy pass performed during EUS at the time of re-staging after chemotherapy, exclusively for research purposes (RNA-seq). All patients undergo standard longitudinal clinical monitoring to assess Progression-Free Survival (PFS) and Overall Survival (OS) for a total period of 30 months or until death.
Primary Objective:
To identify baseline transcriptomic signatures associated with treatment response to mFOL, NG, and PAXG in advanced PDAC patients.
Primary Endpoint:
Response to treatment assessed every 3 months by RECIST 1.1 criteria and defined as Disease Control Rate at 6 months (DCR-6); Progression-Free Survival (PFS) and Overall Survival (OS) during the follow-up period.
Secondary Objectives:
To investigate the longitudinal evolution of PDAC signatures during treatment
Secondary Endpoints:
Comparison of transcriptome signatures between baseline EUS-biopsy and repeated biopsy after 6 months of treatment.
To evaluate the impact of active smoking on transcriptomic subtypes and treatment outcomes via correlation between smoking status and the distribution of classical vs. basal-like subtypes and clinical outcomes.
To compare signatures between primary and metastatic sites throughout the comparison of transcriptomic patterns between primary tumor and metastatic biopsy samples.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with pancreatic adenocarcinoma | – | Procedure: Endoscopic Ultrasound with FNA/FNBThe study population consists of adult patients (aged ≥18 years) with a clinical and/or radiological suspicion of Pancreatic Ductal Adenocarcinoma (PDAC) who are scheduled to undergo a diagnostic Endoscopic Ultrasound-guided Tissue Acquisition (EUS-TA) as part of their standard clinical pathway. The population will include both men and women, without restrictions on ethnicity. Including a 10% loss to follow-up, the planned cohort is 150 patients, evenly distributed among the three regimens (mFOL, NG or PAXG). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population consists of adult patients (aged ≥18 years) with a clinical and/or radiological suspicion of Pancreatic Ductal Adenocarcinoma (PDAC) who are scheduled to undergo a diagnostic Endoscopic Ultrasound-guided Tissue Acquisition (EUS-TA) as part of their standard clinical pathway. The population will include both men and women, without restrictions on ethnicity. Including a 10% loss to follow-up, the planned cohort is 150 patients, evenly distributed among the three regimens (mFOL, NG or PAXG).
Key inclusion criteria (5 listed)
- Age = 18 years
- Willing to sign informed consent
- Patient with CT scan or MRI or EUS with a lesion suspect of PDAC at any clinical stage
- Patients considered fit to receive polychemotherapy with either mFOL, NG or PAXG.
- Patients primarily followed at HSR
Key exclusion criteria (5 listed)
- Patients not willing to sign informed consent
- Pregnancy and breastfeeding
- Cytology positive for malignancies other than PDAC
- Patients who have not performed biopsy for safety or technical reasons
- Patients unfit for polychemotherapy
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 |
|---|---|---|
| Endoscopic Ultrasound with FNA/FNBAfter identification of the mass lesion, a tumor sample will be acquired with a standard FNA/FNB needle, as the standard procedure requires. The sample will be taken and stored in a Eppendorf Tube of 1.5ml pre-filled with 300μL 1-Thioglycerol/Homogenization solution _Promega® then stored in a 80°C freezer and transferred every 2 weeks to the CRB for subsequent RNA-seq. | Procedure or surgery | Patients with pancreatic adenocarcinoma |
Primary outcome
Response to treatment at 6 months
Time frame: 6 months
Response to treatment assessed every 3 months by RECIST 1.1 criteria and defined as Disease Control Rate at 6 months (DCR-6)
Progression-Free Survival (PFS)
Time frame: 30 months
Time of disease progression (PFS)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Background: PubMed 41275879Reni M, Macchini M, Orsi G, Procaccio L, Malleo G, Carconi C, Rapposelli IG, Bencardino K, Scartozzi M, Balzano G, Tamburrino D, Merelli B, Sperti E, Belfiori G, Liscia N, Bozzarelli S, Di Marco M, Tamburini E, Milella M, Lonardi S, Ercolani G, Mazzola M, Palumbo D, Torri V, Falconi M. Preoperative mFOLFIRINOX versus PAXG for stage I-III resectable and borderline resectable pancreatic ductal adenocarcinoma (PACT-21 CASSANDRA): results of the first randomisation analysis of a randomised, open-label, 2 x 2 factorial phase 3 trial. Lancet. 2026 Dec 20;406(10522):2945-2956. doi: 10.1016/S0140-6736(25)01685-X. Epub 2025 Nov 20.
- Background: PubMed 33159833Panzeri V, Manni I, Capone A, Naro C, Sacconi A, Di Agostino S, de Latouliere L, Montori A, Pilozzi E, Piaggio G, Capurso G, Sette C. The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma. Mol Oncol. 2021 Feb;15(2):579-595. doi: 10.1002/1878-0261.12847. Epub 2020 Nov 24.
- Background: PubMed 33266052Archibugi L, Ruta V, Panzeri V, Redegalli M, Testoni SGG, Petrone MC, Rossi G, Falconi M, Reni M, Doglioni C, Sette C, Arcidiacono PG, Capurso G. RNA Extraction from Endoscopic Ultrasound-Acquired Tissue of Pancreatic Cancer Is Feasible and Allows Investigation of Molecular Features. Cells. 2020 Nov 30;9(12):2561. doi: 10.3390/cells9122561.
- Individual participant dataSharing planned: Undecided. data might be shared upon reasonable requests
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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.
Laura Apadula, Research Nurse contact
Laura Apadula, Nurse study chair
IRCCS San Raffaele
Questions about this trial
What is this clinical trial studying?
An observational study of Pancreatic Cancer, run by IRCCS San Raffaele.
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 5 inclusion and 5 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: opening soon, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gabriele Capurso, MD, PhD (00390226436548, capurso.gabriele@hsr.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response to treatment at 6 months (time frame: 6 months). The study lists 2 primary outcomes in all. 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 NCT07794969, which also lists 3 linked publications.
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 31 Aug 2026; AzTrials last refreshed its copy on 7 Nov 2026.