Adjuvant Trial in Patients With Resected PDAC Randomized to Allocation of Oxaliplatin- or Gemcitabine-based Chemotherapy by Standard Clinical Criteria or by a Transcriptomic Treatment Specific Stratification Signature
- Conditions
- Pancreatic Ductal Adenocarcinoma
- Interventions
- Registration Number
- NCT05314998
- Lead Sponsor
- John Neoptolemos
- Brief Summary
This is a multicentre open labelled phase III adjuvant trial of disease-free survival in patients with resected pancreatic ductal adenocarcinoma randomized to allocation of oxaliplatin- or gemcitabine-based chemotherapy by standard clinical criteria (control arm) or by a transcriptomic treatment specific stratification signature or TSS (test arm).
- Detailed Description
The main purpose and primary objective of the study is to determine whether disease free survival in patients with resected pancreatic ductal adenocarcinoma (PDAC) treated with standard adjuvant chemotherapy regimens (oxaliplatin- or gemcitabine-based), is superior using allocation based on a treatment specific signature (TSS), compared to the same chemotherapy regimens allocated according to standard clinical criteria.
Secondary objectives of the study are to assess overall survival (median, 3 year survival rate), metastasis free survival; survival based on targeted signatures (TSS) in test versus control arms, and survival using targeted therapies initially on relapse compared to standard first-line therapies on relapse.
In addition, ESPAC-6 optional translational research programme will obtain tumor specimens and blodd samples to identify biomarkers that may predict response to chemotherapy or relapse.
ESPAC-6 will also generate a biobank of matched patient-derived organoids (PDOs) to provide an experimentally tractable model system for the development and testing of biomarker-driven personalised therapies.
ESPAC-6 translational research programme, will also develop a longitudinal blood biobank to analyse clinically relevant circulating biomarkers, such as blood proteins, metabolites and/or circulating-free tumour DNA.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 394
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria Capecitabine mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to standard clinical criteria or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to standard clinical criteria Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature Gemcitabine mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to individual transcriptomic treatment specific signature or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to individual transcriptomic treatment specific signature Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria Folinic acid mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to standard clinical criteria or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to standard clinical criteria Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria 5-fluorouracil mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to standard clinical criteria or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to standard clinical criteria Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria Gemcitabine mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to standard clinical criteria or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to standard clinical criteria Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature Capecitabine mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to individual transcriptomic treatment specific signature or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to individual transcriptomic treatment specific signature Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria Oxaliplatin mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to standard clinical criteria or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to standard clinical criteria Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria Irinotecan mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to standard clinical criteria or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to standard clinical criteria Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature Irinotecan mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to individual transcriptomic treatment specific signature or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to individual transcriptomic treatment specific signature Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature Oxaliplatin mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to individual transcriptomic treatment specific signature or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to individual transcriptomic treatment specific signature Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature Folinic acid mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to individual transcriptomic treatment specific signature or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to individual transcriptomic treatment specific signature Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature 5-fluorouracil mFOLFIRINOX-therapy (5-FU, Folinic Acid, Irinotecan, Oxaliplatin) according to individual transcriptomic treatment specific signature or Gem/Cap-therapy (Gemcitabine and Capecitabine) according to individual transcriptomic treatment specific signature
- Primary Outcome Measures
Name Time Method Disease free survival 76 months Disease free survival will be defined as time from ramdomisation to disease recurrence (growth or metastasis) or death from any cause all patients fulfilling the in- and exclusion criteria.
- Secondary Outcome Measures
Name Time Method Overall survival 76 months Overall survival is defined as the time from randomization to death due to any cause. If a patient is lost to follow up, overall survival time is censored at the time of last contact.
Metastasis free survival 76 months Metastasis free survival is defined as the time from randomization to detection of metastasis or death from any cause. The time of metastasis is defined as the date of metastasis determined and recorded by the Pancreas Tumour Board (Multidisciplinary Team).
If the patient is eligible for first line therapy the recurrence must be performed by a positive biopsy or cytology.
If a patient is lost to follow up, metastasis free survival time is censored at the time of last contact.Overall survival from recurrence 76 months Overall survival is defined as the time from recurrence to death due to any cause. If a patient is lost to follow up, overall survival time is censored at the time of last contact.
Quality of life (QoL EORTC QLQ-C-30) 76 months QoL will be assessed by the EORTC QLQ-C30 questionnaire in its most current version every three months starting from V1.
Safety: (serious) adverse events and Grade 3 and 4 toxicities according to NCI-CTC v.5.0. 47 months Safety assessments will include adverse events. The proportion of grade 3 and 4 toxicity will be compared across treatments using time to event methods and frequency counts. Adverse and serious adverse events are collected throughout the study and will be tabulated and compared between study arms.
The analysis of all safety endpoints is conducted on the safety set, which contains all patients who received at least one cycle of treatment.
Trial Locations
- Locations (33)
Universitätsklinikum Augsburg, III. medizinische Klinik
🇩🇪Augsburg, Germany
DIK Deggendorf, Onkologische Ambulanz
🇩🇪Deggendorf, Germany
Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,
🇩🇪Frankfurt, Germany
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II und Klinik für Allgemeine Viszeral Gefäß und Kinderchirurgie
🇩🇪Homburg/Saar, Germany
UKSH Campus Kiel, Medizinische Klinik II
🇩🇪Kiel, Germany
Norrlands universitetssjukhus
🇸🇪Umeå, Sweden
Universitätsklinikum Mannheim, II. medizinische Klinik, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Ernährungsmedizin
🇩🇪Mannheim, Germany
Universität Leipzig, Medizinische Fakultät, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Pneumologie
🇩🇪Leipzig, Germany
Universitätsklinikum Schleswig-Holstein, Klinik für Chirurgie, Onkologisches Zentrum Campus Lübeck
🇩🇪Lübeck, Germany
Skånes universitetssjukhus
🇸🇪Lund, Sweden
Universitätsklinikum Marburg, Klinik für Innere Medizin, Gastroenterologie, Stoffwechsel und Endokrinologie
🇩🇪Marburg, Germany
Akademiska sjukhuset
🇸🇪Uppsala, Sweden
Centralsjukhuset
🇸🇪Karlstad, Sweden
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie
🇩🇪Dresden, Germany
Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie
🇩🇪Regensburg, Germany
Universitätsmedizin Rostock, Klinik III (Hämatologie, Onkologie, Palliativmedizin), Zentrum für Innere Medizin
🇩🇪Rostock, Germany
Caritasklinikum Saarbrücken St. Theresia
🇩🇪Saarbrücken, Germany
Universitätsklinikum Aachen, Studienzentrum Viszeralmedizin Klinik für Allgemeine-, Viszeral und Transplatationschirurgie
🇩🇪Aachen, Germany
St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Studienambulanz
🇩🇪Bochum, Germany
Universitätsklinikum Bonn, Chirurgische Abteilung
🇩🇪Bonn, Germany
Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien
🇩🇪Erlangen, Germany
Universitätsklinikum Freiburg, Klinik für Allgemein und Viszeralchirurgie, Abteilung Chirurgie
🇩🇪Freiburg, Germany
Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin I
🇩🇪Halle (Saale), Germany
Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
🇩🇪Hannover, Germany
Universitätsklinikum Hamburg Eppendort, Zentrum für operative Medizin, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie
🇩🇪Hamburg, Germany
Univeristätsklinikum Jena
🇩🇪Jena, Germany
Universitätsklinikum Heidelberg, Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie und Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie
🇩🇪Heidelberg, Germany
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum für Innere Medizin
🇩🇪Würzburg, Germany
Universitätsklinikum Ulm, Klinik für Innere Medizin I Gastroenterologie-Endokrinologie-, Nephrologie-, Ernährung und Stoffwechselkrankheiten
🇩🇪Ulm, Germany
Universitetssjukhuset
🇸🇪Linköping, Sweden
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. medizinische Klinik, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
🇩🇪Mainz, Germany
Klinikum der Universität München, AG Onkologie der Med Klinik III
🇩🇪München, Germany
Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Chirurgie
🇩🇪München, Germany