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JOURNAL ONKOLOGIE – STUDIE

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

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NCT-Nummer:
NCT05314998

Studienbeginn:
April 2024

Letztes Update:
20.03.2024

Wirkstoff:
Oxaliplatin, Irinotecan, Folinic Acid, 5-Fluorouracil, Gemcitabine, Capecitabine

Indikation (Clinical Trials):
Adenocarcinoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
John Neoptolemos

Collaborator:
Molecular Health GmbH, Deutsches Krebsforschungszentrum (DKFZ), Nationales Centrum für Tumorerkrankungen, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest, Institut für Medizinische Biometrie,

Studienleiter

John Neoptolemos, Prof. Dr.
Study Director
Universität Heidelberg

Kontakt

John Neoptolemos, Prof. Dr.
Kontakt:
Phone: 0049 6221 56-39020
E-Mail: john.neoptolemos@med.uni-heidelberg.de» Kontaktdaten anzeigen

Studienlocations
(3 von 33)

Universitätsklinikum Aachen, Studienzentrum Viszeralmedizin Klinik für Allgemeine-, Viszeral und Transplatationschirurgie
52074 Aachen
Germany» Google-Maps
Universitätsklinikum Augsburg, III. medizinische Klinik
86156 Augsburg
(Bayern)
Germany» Google-Maps
St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Studienambulanz
44791 Bochum
(Nordrhein-Westfalen)
Germany» Google-Maps
Universitätsklinikum Bonn, Chirurgische Abteilung
53127 Bonn
(Nordrhein-Westfalen)
Germany» Google-Maps
DIK Deggendorf, Onkologische Ambulanz
94469 Deggendorf
(Bayern)
Germany» Google-Maps
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie
01307 Dresden
(Sachsen)
Germany» Google-Maps
Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien
91054 Erlangen
(Bayern)
Germany» Google-Maps
Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,
60590 Frankfurt
(Hessen)
Germany» Google-Maps
Universitätsklinikum Freiburg, Klinik für Allgemein und Viszeralchirurgie, Abteilung Chirurgie
79106 Freiburg
(Baden-Württemberg)
Germany» Google-Maps
Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin I
06120 Halle (Saale)
(Sachsen-Anhalt)
Germany» Google-Maps
Universitätsklinikum Hamburg Eppendort, Zentrum für operative Medizin, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie
20246 Hamburg
(Hamburg)
Germany» Google-Maps
Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie
30625 Hannover
(Niedersachsen)
Germany» Google-Maps
Universitätsklinikum Heidelberg, Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie und Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie
69120 Heidelberg
(Baden-Württemberg)
Germany» Google-Maps
Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II und Klinik für Allgemeine Viszeral Gefäß und Kinderchirurgie
66421 Homburg/Saar
(Saarland)
Germany» Google-Maps
UKSH Campus Kiel, Medizinische Klinik II
24105 Kiel
(Schleswig-Holstein)
Germany» Google-Maps
Universität Leipzig, Medizinische Fakultät, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Pneumologie
04103 Leipzig
(Sachsen)
Germany» Google-Maps
Universitätsklinikum Schleswig-Holstein, Klinik für Chirurgie, Onkologisches Zentrum Campus Lübeck
23538 Lübeck
(Schleswig-Holstein)
Germany» Google-Maps
Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. medizinische Klinik, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie
55131 Mainz
(Rheinland-Pfalz)
Germany» Google-Maps
Universitätsklinikum Mannheim, II. medizinische Klinik, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Ernährungsmedizin
68167 Mannheim
(Baden-Württemberg)
Germany» Google-Maps
Universitätsklinikum Marburg, Klinik für Innere Medizin, Gastroenterologie, Stoffwechsel und Endokrinologie
35043 Marburg
(Hessen)
Germany» Google-Maps
Klinikum der Universität München, AG Onkologie der Med Klinik III
81377 München
(Bayern)
Germany» Google-Maps
Klinikum Rechts der Isar der TU München, Klinik und Poliklinik für Chirurgie
81675 München
(Bayern)
Germany» Google-Maps
Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie
93053 Regensburg
(Bayern)
Germany» Google-Maps
Universitätsmedizin Rostock, Klinik III (Hämatologie, Onkologie, Palliativmedizin), Zentrum für Innere Medizin
18055 Rostock
(Mecklenburg-Vorpommern)
Germany» Google-Maps
Caritasklinikum Saarbrücken St. Theresia
66113 Saarbrücken
(Saarland)
Germany» Google-Maps
Universitätsklinikum Ulm, Klinik für Innere Medizin I Gastroenterologie-Endokrinologie-, Nephrologie-, Ernährung und Stoffwechselkrankheiten
89081 Ulm
(Baden-Württemberg)
Germany» Google-Maps
Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum für Innere Medizin
97080 Würzburg
(Bayern)
Germany» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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

Studien-Rationale

Primary outcome:

1. Disease free survival (Time Frame - 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:

1. Overall survival (Time Frame - 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.

2. Metastasis free survival (Time Frame - 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.

3. Overall survival from recurrence (Time Frame - 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.

4. Quality of life (QoL EORTC QLQ-C-30) (Time Frame - 76 months):
QoL will be assessed by the EORTC QLQ-C30 questionnaire in its most current version every three months starting from V1.

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

Studien-Arme

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

Geprüfte Regime

  • Oxaliplatin:
    85 mg/m2 D1 over 2 hours every; 14 days, 12 cycles, 24 weeks
  • Irinotecan:
    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
  • Folinic acid:
    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
  • 5-fluorouracil:
    2.4 g/m2 IV continuous infusion over 46 hours (1200 mg/m2/ day); every 14 days, 12 cycles, 24 weeks
  • Gemcitabine:
    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
  • Capecitabine:
    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

Quelle: ClinicalTrials.gov


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