Liquid Biopsy (ctDNA) Guided Treatment in Localized Pancreatic Cancer: Neoadjuvant CTX vs. Upfront Surgery (LIQUIPANC)

Liquid Biopsy Guided Treatment in Localized Pancreatic Cancer (LIQUIPANC): Circulating Tumor DNA (ctDNA) as Precision Medicine Tool for Stratification of Neoadjuvant Chemotherapy vs. Upfront Surgery

This study evaluates the clinical prognostic impact (on DFS and OS) of liquid biopsy guided treatment vs. standard of care (physicians choice) in localized pancreatic cancer (despite because of CA 19-9 levels and computed tomography, upfront surgery is recommended by tumor board). ctDNA positive patients will receive neoadjvuant chemotherapy at current gold standard physicians choice instead of upfront surgery, because of assumed high biological risk for early recurrence.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer; Circulating Tumor Cell; Predictive Cancer Model
• Intervention / Treatment: Procedure: Neoadjuvant chemotherapy instead of upfront surgery; Procedure: Upfront surgery

Detailed Description

Pancreatic cancer (PC) bears dramatically high relapse rates with consecutive low 5-year survival rates (4.2% over all tumor stages and 0.5% in stage IV disease) despite major improvements of interdisciplinary perioperative management and more aggressive surgical approaches to enable potentially curative pancreatic surgery. PC is estimated to represent the second most cancer associated cause of death by 2030 worldwide. Circulating tumor DNA (ctDNA) has been outpointed to be a promising prognostic marker for several malignant diseases. In precursor studies, the investigators have shown (a) a definitive cut-off (42% decrease from the baseline) for the relative change of ctDNA after only 2 weeks of systemic chemotherapy to reliably (specificity 100%, sensitivity 91.7%) predict response to treatment at a median of 10 weeks earlier (80% faster) than current gold standard (computed tomography after 3 months of treatment) via simple blood collection and consecutive molecular analysis via ddPCR (Kirchweger et al., Frontiers in Oncology, 08/22), which could allow an early change of treatment regimen in the future in order to improve patients survival and decrease the amount of unevaluated cytotoxic agents. Furthermore, the investigators could show (b) that pretherapeutic detectable ctDNA in localized PC could reliably indicate early distant relapse (DFS 3.3 vs. 18.1 months) despite no radiological evidence of advanced or disseminated disease prior to surgery (Kirchweger et al., European Journal of Surgical Oncology, 12/21). All patients in this study suffering from early relapse went through interdisciplinary tumor boards and did not receive neoadjuvant chemotherapy because of radiological resectability and CA 19-9 values within the normal range (<500kU/l). ctDNA on the other hand bears the potential to differentiate localized from disseminated disease.

The planned project aims to prove a clinical applicable easily assessable and minimal invasive approach (mere blood collection during clinical routine) of molecular testing in the periphery to distinguish localized from disseminated disease in pancreatic cancer patients to highly individually stratify for neoadjuvant chemotherapy or upfront surgery on a (molecular)-biological base with a high sensitive method to oppose current difficulties of detection rates in PC in addition to current gold standard of radiological staging in the future.

The investigators will take approximately 30ml of blood (simple blood puncture) from patients with localized pancreatic cancer who have undergone full staging procedure and have been recommended upfront surgery by interdisciplinary tumor board. ddPCR will be performed by testing KRAS G12/13 and, if negative, KRAS Q61 preoperatively. ctDNA positive patients will be distributed to either observation group (standard of care - upfront surgery) or personalized treatment group (LB informed treatment decisions - neoadjuvant/adjuvant chemotherapy).

Treatment groups will be compared for PFS and OS.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Patrick Kirchweger, MD, PhD; Phone Number: +436644159646; Email: patrick.kirchweger@ordensklinikum.at
• Study Contact Backup: Name: Helwig Wundsam, PD, MD; Phone Number: +4373276774562; Email: helwig.wundsam@ordensklinikum.at

Study Locations

• Austria
  • Upper Austria
    • Linz, Upper Austria, Austria, 4010
      • Recruiting
      • Ordensklinikum Linz Barmherzige Schwestern
      • Contact: Patrick Kirchweger, MD, PhD; Phone Number: +436644159646; Email: patrick.kirchweger@ordensklinikum.at
      • Contact: Helwig Wundsam, PD, MD; Phone Number: +4373276774562; Email: helwig.wundsam@ordensklinikum.at

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent
• >18 years old
• localized pancreatic cancer to go for upfront surgery

Exclusion Criteria:

• synchronous secondary malignancy
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ctDNA guided; All patients included into the study are recommended to go for upfront surgery (localized and resectable tumor in CT and CA19-9 <500kU/l) by tumor board. If preoperative ctDNA in peripheral blood is positive, we assume high risk for early recurrence (because of systemic tumor burden) and apply neoadjuvant chemotherapy at physicians choice instead.	Procedure: Neoadjuvant chemotherapy instead of upfront surgery; All patients included into the study are recommended to go for upfront surgery (CT and CA19-9) by tumor board. If preoperative ctDNA is positive, the investigators assume high risk for early recurrence (because of systemic tumor burden) and apply neoadjuvant chemotherapy at physicians choice instead.; Apart from blood collection (within the scope of clinical routine), there is no additional diagnostic intervention performed on the patient.; The respective neoadjuvant chemotherapeutical drug will be selected and applied by the treating medical oncologist at physicians choice (unaffected by study participation), usually mFOLFIRINOX or Gemcitabine/nabPaclitaxel at standardized dosage recommended by NCCN and local guidelines. FOLFIRONOX: Folinic acid (also known as leucovorin), F - Fluorouracil (5-FU), IRIN - Irinotecan, OX - Oxaliplatin.; Other Names: Experimental
Other: Standard of care; Patient get the gold standard treatment at physicians choice, independent to study participation (here the study is just observational).	Procedure: Upfront surgery; Standard of care as recommended by tumor board (not affected by study conditions).; Other Names: Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS	Disease free survival	After 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival	After 12 months
ctDNA detection rate	Detection rate of ctDNA in peripheral blood using a cost-effective and clinical applicable small spectrum ddPCR analysis in order to enable immediate clinical implementation	Preoperatively

Collaborators and Investigators

• Sponsor: Elisabethinen Hospital
• Collaborators: Medical University Innsbruck
• Investigators: Principal Investigator: Patrick Kirchweger, MD, PhD, Ordensklinikum Linz, Department of Surgery

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 20, 2024
• First Submitted That Met QC Criteria: April 25, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Neoplastic Processes; Pancreatic Diseases; Neoplasm Metastasis; Pancreatic Neoplasms; Neoplastic Cells, Circulating
• Other Study ID Numbers: 1199/2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No