Implementing ctDNA and Circular DNA in Patients With Localized Pancreatic Cancer

Study Overview
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Brief Summary
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The goal of this clinical trial is to investigate if plasma ctDNA and eccDNA before resection for suspicion of pancreatic ductal adenocarcinoma (PDAC) can predict early recurrence and overall survival, and to investigate if plasma ctDNA combined with CT scan and endoscopic ultrasound surveillance increases the median overall survival compared with standard-of-care surveillance.

Detailed Description
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The aim of the CIRCPAC study is to evaluate if plasma ctDNA from patients scheduled for surgical resection of PDAC can identify patients who will benefit from surgery and if plasma ctDNA can identify recurrence earlier and improve the survival and quality of life of the patients compared with standard-of-care surveillance. Patients operated for PDAC will be included in this Danish multicenter study including an observational study (Sub-study 1: 700 patients) and an interventional randomized trial (Sub-study 2: 410 patients). In Sub-study 1, patients will have blood samples drawn prior to surgery, 4 weeks after surgery, and 6 months after surgery. In Sub-study 2, patients without recurrence 4 months after surgery, will be randomized in a 1:1 manor to an experimental arm (arm A) with ctDNA guided surveillance, or to a control arm (B) with standard surveillance.

Official Title
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Implementing Non-invasive Circulating Tumor DNA and Circular DNA Analysis in Patients With Localized Pancreatic Cancer to Optimize the Pre- and Postoperative Treatment: Predicting Recurrence and Survival and Changing Prognosis Over Time

Conditions
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Resectable Pancreatic Cancer

Intervention / Treatment
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* Diagnostic Test: ctDNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sub-study 1: Suspicion of PDAC tumor stage I-III, scheduled for pancreatic resection, with or without preoperative neoadjuvant chemotherapy. Sub-study 2: . PDAC tumor stage I-III Has received intended curative resection (R0/R1) of PDAC No signs of local recurrence or metastatic disease at a CT scan 4 months after the operation Exclusion Criteria: Other cancers (excluding skin cancer other than melanoma) later than 3 years before inclusion Patients who are unlikely to comply with the protocol, inability to return for subsequent visits) and/or otherwise considered by the Investigator to be unlikely to complete the study
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A: Experimental<br>Patients will receive surveillance with liver enzymes, CA 19-9, history, clinical evaluation of signs of recurrence (e.g. weight loss, abdominal pain or fatigue) in combination with analysis of plasma ctDNA (90 ml blood drawn per visit) every 3 months until disease progression or up to 36 months. If plasma ctDNA is positive the patient will have a CT scan (thorax and abdomen) and EUS every 3 months for 2 years and then every 6 months until disease recurrence or up to 36 months. If plasma ctDNA is negative the patient will have CT scan of thorax and abdomen and EUS every 6 months until disease recurrence or up to 36 months. Plasma eccDNA will be determined at the same time as ctDNA but a positive eccDNA result will not be informed to the patients. | Diagnostic Test: ctDNA<br>* ctDNA guided surveillance<br>* Other names: eccDNA;|
| No Intervention: B: Control<br>Patients will receive surveillance until recurrence according to current Danish guidelines with liver enzymes, history and clinical evaluation every 3 months for two years and then every 6 months until 36 months. If an increase in liver enzymes is seen or clinical signs of recurrence (e.g. weight loss, abdominal pain or fatigue) patients will have a CT scan of thorax and abdomen. Blood samples (90 ml blood per visit) will be collected at the same time points as blood is drawn for liver enzymes (i.e. every 6 months until 36 months) for later analysis at the end of study of plasma ctDNA and eccDNA. These measurements will serve to enable post-trial comparison of oncological outcomes for the two arms. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sub-study 1 ctDNA | Preoperative plasma ctDNA levels before PDAC resection predicting early recurrence. | 36 months | 
| Sub-study 1 eccDNA | Preoperative plasma eccDNA levels before PDAC resection predicting early recurrence. | 36 months | 
| Sub-study 2 ctDNA DFS | Number of patients with recurrence assessed by ctDNA | 3 years from surgery for PDAC | 
| Sub-study 2 ctDNA OS | Overall survival of patients in arm A compared with patients in Arm B | 3 years from surgery for PDAC | 
| Sub-study 2 eccDNA | Number of patients with recurrence assessed by eccDNA | 3 years from surgery for PDAC |