Clinical trial NCT05314998: 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
Official title: An 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 or by a Transcriptomic Treatment Specific Stratification Signature
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Pancreatic Ductal Adenocarcinoma
Keywords: Pancreatic Ductal Adenocarcinoma
PDAC
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Molecular Health GmbH
name: German Cancer Research Center
name: Nationales Centrum für Tumorerkrankungen
name: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
name: Institut für Medizinische Biometrie
First posted: 2022-04-07
Enrollment: 394
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria

1. Histologically proven pancreatic ductal adenocarcinoma including variants, and pancreatic acinar cell carcinoma.
2. Patient had provided tumour tissue at resection for RNAseq.
3. Macroscopically complete resection (R0 or R1 resection).
4. Female and male Patients aged from 18 to 79 years.
5. WHO performance status 0-1.
6. No prior radiotherapy and no previous chemotherapy for pancreatic cancer.
7. 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.
8. Adequate hematologic function: Absolute neutrophil count ≥ 1,500 cells/mm3, platelets ≥ 100,000 cells/mm3 and haemoglobin ≥ 8 g/L (transfusion permitted).
9. Serum total bilirubin ≤ 1.5 times the institutional upper limit of normal.
10. Creatinine clearance ≥ 50 mL/min.
11. 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.
12. Intended interval since surgery between 21 and 84 days at date of randomization.
13. Public or private health insurance cover.
14. Ability of subject to understand character and individual consequences of the clinical trial.
15. Not legally incapacitated.
16. Written informed consent.

Exclusion Criteria

1. Solid pseudopapillary neoplasm, neuroendocrine neoplasm, pancreatoblastoma, bile duct cancer, and ampullary cancer.
2. Distant metastases, including ascites or malignant pleural effusion.
3. Macroscopic incomplete tumour removal (R2 resection).
4. Post-operative CA 19-9 \> 180 U / ml before randomization on study.
5. Cardiomyopathy or congestive heart failure, NYHA III-IV or coronary heart disease symptoms.
6. 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.
7. Pre-existing neuropathy, Gilbert's disease or known genotype UGT1A1\*28 /\*28.
8. Inflammatory disease of the colon or rectum, or intestinal obstruction, or severe postoperative uncontrolled diarrhoea.
9. 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)
10. Pregnancy and lactation.
11. Participation in other clinical trials or observation period of competing trials, respectively.
12. 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.
13. 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.
14. Any other concurrent antineoplastic treatment including irradiation

Primary outcomes:
measure: Disease free survival
timeFrame: 76 months
Secondary outcomes:
measure: Overall survival
timeFrame: 76 months
measure: Metastasis free survival
timeFrame: 76 months
measure: Overall survival from recurrence
timeFrame: 76 months
measure: Quality of life (QoL EORTC QLQ-C-30)
timeFrame: 76 months
measure: Safety: (serious) adverse events and Grade 3 and 4 toxicities according to NCI-CTC v.5.0.
timeFrame: 47 months
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: Universitätsklinikum Aachen, Studienzentrum Viszeralmedizin Klinik für Allgemeine-, Viszeral und Transplatationschirurgie
city: Augsburg
country: Germany
facility: Universitätsklinikum Augsburg, III. medizinische Klinik
city: Bochum
country: Germany
facility: St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Studienambulanz
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Chirurgische Abteilung
city: Deggendorf
country: Germany
facility: DIK Deggendorf, Onkologische Ambulanz
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Allgemein und Viszeralchirurgie, Abteilung Chirurgie
city: Halle (Saale)
country: Germany
facility: Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin I
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendort, Zentrum für operative Medizin, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg, Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie und Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie
city: Homburg/Saar
country: Germany
facility: Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II und Klinik für Allgemeine Viszeral Gefäß und Kinderchirurgie
city: Jena
country: Germany
facility: Univeristätsklinikum Jena
city: Kiel
country: Germany
facility: UKSH Campus Kiel, Medizinische Klinik II
city: Leipzig
country: Germany
facility: Universität Leipzig, Medizinische Fakultät, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Pneumologie
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Klinik für Chirurgie, Onkologisches Zentrum Campus Lübeck
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. medizinische Klinik, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim, II. medizinische Klinik, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Ernährungsmedizin
city: Marburg
country: Germany
facility: Universitätsklinikum Marburg, Klinik für Innere Medizin, Gastroenterologie, Stoffwechsel und Endokrinologie
city: München
country: Germany
facility: Klinikum der Universität München, AG Onkologie der Med Klinik III
city: München
country: Germany
facility: Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Chirurgie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock, Klinik III (Hämatologie, Onkologie, Palliativmedizin), Zentrum für Innere Medizin
city: Saarbrücken
country: Germany
facility: Caritasklinikum Saarbrücken St. Theresia
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Klinik für Innere Medizin I Gastroenterologie-Endokrinologie-, Nephrologie-, Ernährung und Stoffwechselkrankheiten
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum für Innere Medizin
city: Karlstad
country: Sweden
facility: Centralsjukhuset
city: Linköping
country: Sweden
facility: Universitetssjukhuset
city: Lund
country: Sweden
facility: Skånes universitetssjukhus
city: Umeå
country: Sweden
facility: Norrlands universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset
Study officials:
affiliation: Universität Heidelberg
name: John Neoptolemos, Prof. Dr.
role: STUDY_DIRECTOR
References: