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

NCT ID: NCT05314998

Last Updated: 2024-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

394 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-01-15

Study Completion Date

2031-09-01

Brief Summary

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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

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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.

Conditions

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Pancreatic Ductal Adenocarcinoma

Keywords

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Pancreatic Ductal Adenocarcinoma PDAC

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Oxaliplatin

Intervention Type DRUG

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

Irinotecan

Intervention Type 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

Folinic acid

Intervention Type 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

5-fluorouracil

Intervention Type DRUG

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

Gemcitabine

Intervention Type 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

Capecitabine

Intervention Type 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

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

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

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

Irinotecan

Intervention Type 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

Folinic acid

Intervention Type 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

5-fluorouracil

Intervention Type DRUG

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

Gemcitabine

Intervention Type 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

Capecitabine

Intervention Type 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

Interventions

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Oxaliplatin

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

5-fluorouracil

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

Intervention Type DRUG

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

Intervention Type DRUG

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

79 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Molecular Health GmbH

INDUSTRY

Sponsor Role collaborator

German Cancer Research Center

OTHER

Sponsor Role collaborator

Nationales Centrum für Tumorerkrankungen

UNKNOWN

Sponsor Role collaborator

Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

OTHER

Sponsor Role collaborator

Institut für Medizinische Biometrie

UNKNOWN

Sponsor Role collaborator

John Neoptolemos

OTHER

Sponsor Role lead

Responsible Party

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John Neoptolemos

Prof. Dr. med.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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John Neoptolemos, Prof. Dr.

Role: STUDY_DIRECTOR

Universität Heidelberg

Locations

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

Aachen, , Germany

Site Status

Universitätsklinikum Augsburg, III. medizinische Klinik

Augsburg, , Germany

Site Status

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

Bochum, , Germany

Site Status

Universitätsklinikum Bonn, Chirurgische Abteilung

Bonn, , Germany

Site Status

DIK Deggendorf, Onkologische Ambulanz

Deggendorf, , Germany

Site Status

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

Dresden, , Germany

Site Status

Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien

Erlangen, , Germany

Site Status

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

Frankfurt, , Germany

Site Status

Universitätsklinikum Freiburg, Klinik für Allgemein und Viszeralchirurgie, Abteilung Chirurgie

Freiburg im Breisgau, , Germany

Site Status

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

Halle, , Germany

Site Status

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

Hamburg, , Germany

Site Status

Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie

Hanover, , Germany

Site Status

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

Heidelberg, , Germany

Site Status

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

Homburg/Saar, , Germany

Site Status

Univeristätsklinikum Jena

Jena, , Germany

Site Status

UKSH Campus Kiel, Medizinische Klinik II

Kiel, , Germany

Site Status

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

Leipzig, , Germany

Site Status

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

Lübeck, , Germany

Site Status

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

Mainz, , Germany

Site Status

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

Mannheim, , Germany

Site Status

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

Marburg, , Germany

Site Status

Klinikum der Universität München, AG Onkologie der Med Klinik III

München, , Germany

Site Status

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

München, , Germany

Site Status

Universitätsklinikum Regensburg, Klinik und Poliklinik für Chirurgie

Regensburg, , Germany

Site Status

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

Rostock, , Germany

Site Status

Caritasklinikum Saarbrücken St. Theresia

Saarbrücken, , Germany

Site Status

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

Ulm, , Germany

Site Status

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

Würzburg, , Germany

Site Status

Centralsjukhuset

Karlstad, , Sweden

Site Status

Universitetssjukhuset

Linköping, , Sweden

Site Status

Skånes universitetssjukhus

Lund, , Sweden

Site Status

Norrlands universitetssjukhus

Umeå, , Sweden

Site Status

Akademiska sjukhuset

Uppsala, , Sweden

Site Status

Countries

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Germany Sweden

Central Contacts

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John Neoptolemos, Prof. Dr.

Role: CONTACT

Phone: 0049 6221 56-39020

Email: [email protected]

Claudia Pauligk, Dr.

Role: CONTACT

Phone: 0049 69 6301 - 3906

Email: [email protected]

Other Identifiers

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AIO-PAK-0121/ass

Identifier Type: OTHER

Identifier Source: secondary_id

2020-004906-79

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ESPAC-6

Identifier Type: -

Identifier Source: org_study_id