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

NCT05314998 | Not Yet Recruiting Phase 3 DMC

• 3 other identifiers: ESPAC-6AIO-PAK-0121/ass2020-004906-79
• Study Type: interventional
• Target: 394
• Locations: 2 countries
• Sites: 33

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).

Conditions

Pancreatic Ductal Adenocarcinoma

Keywords

Pancreatic Ductal Adenocarcinoma; PDAC

Outcome Measures

Primary Outcomes (1)

• Disease free survival

  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.

  76 months

Secondary Outcomes (5)

• Overall survival

  76 months

• Metastasis free survival

  76 months

• Overall survival from recurrence

  76 months

• Quality of life (QoL EORTC QLQ-C-30)

  76 months

• Safety: (serious) adverse events and Grade 3 and 4 toxicities according to NCI-CTC v.5.0.

  47 months

Study Arms (2)

Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

EXPERIMENTAL

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

Drug: Oxaliplatin; Drug: Irinotecan; Drug: Folinic acid; Drug: 5-fluorouracil; Drug: Gemcitabine; Drug: Capecitabine

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria

ACTIVE COMPARATOR

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

Drug: Oxaliplatin; Drug: Irinotecan; Drug: Folinic acid; Drug: 5-fluorouracil; Drug: Gemcitabine; Drug: Capecitabine

Interventions

Oxaliplatin DRUG

85 mg/m2 D1 over 2 hours every; 14 days, 12 cycles, 24 weeks

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria; Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

Irinotecan DRUG

150 mg/m2 D1 over 90 minutes to begin 30 min after the Folinic acid infusion is started; every 14 days, 12 cycles, 24 weeks

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria; Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

Folinic acid DRUG

400 mg/m2 (racemic mixture) (or 200 mg/m2 if L-folinic acid is used), IV infusion over 2 hours; every 14 days, 12 cycles, 24 weeks

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria; Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

5-fluorouracil DRUG

2.4 g/m2 IV continuous infusion over 46 hours (1200 mg/m2/ day); every 14 days, 12 cycles, 24 weeks

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria; Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

Gemcitabine DRUG

1000mg/m2 is given as an IV infusion over 30 minutes; on day 1, 8 and 15 out of 28 days (= 1 cycle); Repeated 6 times (i.e., 6 cycles) for 24 weeks

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria; Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

Capecitabine DRUG

1660mg/m2/day in two divided doses administered orally for 21 days followed by 7 days' rest (one cycle) for six cycles i.e. 24 weeks

Control Arm B: mFOLFIRINOX or Gem/Cap according to standard clinical criteria; Test Arm A: mFOLFIRINOX or Gem/Cap according to transcriptomic treatment specific signature

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven pancreatic ductal adenocarcinoma including variants, and pancreatic acinar cell carcinoma.
• Patient had provided tumour tissue at resection for RNAseq.
• Macroscopically complete resection (R0 or R1 resection).
• Female and male Patients aged from 18 to 79 years.
• WHO performance status 0-1.
• No prior radiotherapy and no previous chemotherapy for pancreatic cancer.
• Full recovery from surgery and patient able to receive chemotherapy: adequate oral nutrition of ≥ 1500 calories per day and free of significant nausea and vomiting.
• Adequate hematologic function: Absolute neutrophil count ≥ 1,500 cells/mm3, platelets ≥ 100,000 cells/mm3 and haemoglobin ≥ 8 g/L (transfusion permitted).
• Serum total bilirubin ≤ 1.5 times the institutional upper limit of normal.
• Creatinine clearance ≥ 50 mL/min.
• Patient of child-bearing potential (for female patient: study entry after a menstrual period and a negative pregnancy test) must agree to use highly effective methods of contraception during the study and for 6 months after the last study treatment for women and 6 months for men.
• Intended interval since surgery between 21 and 84 days at date of randomization.
• Public or private health insurance cover.
• Ability of subject to understand character and individual consequences of the clinical trial.
• Not legally incapacitated.

You may not qualify if:

• Solid pseudopapillary neoplasm, neuroendocrine neoplasm, pancreatoblastoma, bile duct cancer, and ampullary cancer.
• Distant metastases, including ascites or malignant pleural effusion.
• Macroscopic incomplete tumour removal (R2 resection).
• Post-operative CA 19-9 \> 180 U / ml before randomization on study.
• Cardiomyopathy or congestive heart failure, NYHA III-IV or coronary heart disease symptoms.
• Major comorbidity that may preclude the delivery of treatment or known active infection (HIV or untreated chronic hepatitis B or active hepatitis C) or uncontrolled diabetes.
• Pre-existing neuropathy, Gilbert's disease or known genotype UGT1A1\*28 /\*28.
• Inflammatory disease of the colon or rectum, or intestinal obstruction, or severe postoperative uncontrolled diarrhoea.
• Known severe dihydropyrimidine dehydrogenase (DPD) deficiency (activity score \<1). There are clear guidelines for dose reductions for patients with a score of 1 and 1,5 (2 is normal activity)
• Pregnancy and lactation.
• Participation in other clinical trials or observation period of competing trials, respectively.
• History of hypersensitivity or other known contraindication to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
• Past or current history of other malignancies not curatively treated and without evidence of disease for more than 5 years, except for curatively treated basal cell carcinoma of the skin and in situ carcinoma of the cervix or bladder, or low/intermediate risk prostate cancer (Gleason score ≤7) with normal PSA levels.
• Any other concurrent antineoplastic treatment including irradiation

Sponsors & Collaborators

• John Neoptolemos: lead
• Molecular Health GmbH: collaborator
• German Cancer Research Center: collaborator
• Nationales Centrum für Tumorerkrankungen: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: collaborator
• Institut für Medizinische Biometrie: collaborator

Study Sites (33)

Universitätsklinikum Aachen, Studienzentrum Viszeralmedizin Klinik für Allgemeine-, Viszeral und Transplatationschirurgie

Aachen, 52074, Germany

Location

Universitätsklinikum Augsburg, III. medizinische Klinik

Augsburg, 86156, Germany

Location

St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Studienambulanz

Bochum, 44791, Germany

Location

Universitätsklinikum Bonn, Chirurgische Abteilung

Bonn, 53127, Germany

Location

DIK Deggendorf, Onkologische Ambulanz

Deggendorf, 94469, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie

Dresden, 01307, Germany

Location

Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien

Erlangen, 91054, Germany

Location

Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,

Frankfurt, 60590, Germany

Location

Universitätsklinikum Freiburg, Klinik für Allgemein und Viszeralchirurgie, Abteilung Chirurgie

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin I

Halle, 06120, Germany

Location

Universitätsklinikum Hamburg Eppendort, Zentrum für operative Medizin, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie

Hamburg, 20246, Germany

Location

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, 30625, Germany

Location

Universitätsklinikum Heidelberg, Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie und Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie

Heidelberg, 69120, Germany

Location

Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II und Klinik für Allgemeine Viszeral Gefäß und Kinderchirurgie

Homburg/Saar, 66421, Germany

Location

Univeristätsklinikum Jena

Jena, 07743, Germany

Location

UKSH Campus Kiel, Medizinische Klinik II

Kiel, 24105, Germany

Location

Universität Leipzig, Medizinische Fakultät, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Pneumologie

Leipzig, 04103, Germany

Location

Universitätsklinikum Schleswig-Holstein, Klinik für Chirurgie, Onkologisches Zentrum Campus Lübeck

Lübeck, 23538, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. medizinische Klinik, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie

Mainz, 55131, Germany

Location

Universitätsklinikum Mannheim, II. medizinische Klinik, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Ernährungsmedizin

Mannheim, 68167, Germany

Location

Universitätsklinikum Marburg, Klinik für Innere Medizin, Gastroenterologie, Stoffwechsel und Endokrinologie

Marburg, 35043, Germany

Location

Klinikum der Universität München, AG Onkologie der Med Klinik III

München, 81377, Germany

Location

Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Chirurgie

München, 81675, Germany

Location

Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie

Regensburg, 93053, Germany

Location

Universitätsmedizin Rostock, Klinik III (Hämatologie, Onkologie, Palliativmedizin), Zentrum für Innere Medizin

Rostock, 18055, Germany

Location

Caritasklinikum Saarbrücken St. Theresia

Saarbrücken, 66113, Germany

Location

Universitätsklinikum Ulm, Klinik für Innere Medizin I Gastroenterologie-Endokrinologie-, Nephrologie-, Ernährung und Stoffwechselkrankheiten

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum für Innere Medizin

Würzburg, 97080, Germany

Location

Centralsjukhuset

Karlstad, Sweden

Location

Universitetssjukhuset

Linköping, Sweden

Location

Skånes universitetssjukhus

Lund, Sweden

Location

Norrlands universitetssjukhus

Umeå, Sweden

Location

Akademiska sjukhuset

Uppsala, Sweden

Location

MeSH Terms

Interventions

Oxaliplatin; Irinotecan; Leucovorin; Fluorouracil; Gemcitabine; Capecitabine

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• John Neoptolemos, Prof. Dr.

  Universität Heidelberg

  STUDY DIRECTOR

Central Study Contacts

John Neoptolemos, Prof. Dr.

CONTACT

0049 6221 56-39020; john.neoptolemos@med.uni-heidelberg.de

Claudia Pauligk, Dr.

CONTACT

0049 69 6301 - 3906; pauligk.claudia@ikf-khnw.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. med.

Model Details: Therapeutic intervention of standard adjuvant chemotherapy comprising oxaliplatin- or gemcitabine-based regimens based on standard clinical criteria, compared to selection using a treatment specific signature and prediction model.

Study Record Dates

• First Submitted: March 29, 2022
• First Posted: April 7, 2022
• Study Start: January 15, 2025
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): September 1, 2031
• Last Updated: December 10, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (28); SE (5)