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

Pancreatic Ductal Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05314998
• Other study ID #: ESPAC-6
• Secondary ID: AIO-PAK-0121/ass
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: June 15, 2024
• Est. completion date: September 1, 2031

Study information

• Verified date: May 2024
• Source: Heidelberg University
• Contact: John Neoptolemos, Prof. Dr.
• Phone: 0049 6221 56-39020
• Email: john.neoptolemos[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 394
• Est. completion date: September 1, 2031
• Est. primary completion date: January 1, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
Germany	Universitätsklinikum Aachen, Studienzentrum Viszeralmedizin Klinik für Allgemeine-, Viszeral und Transplatationschirurgie	Aachen
Germany	Universitätsklinikum Augsburg, III. medizinische Klinik	Augsburg
Germany	St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Abteilung für Hämatologie, Onkologie und Palliativmedizin, Studienambulanz	Bochum
Germany	Universitätsklinikum Bonn, Chirurgische Abteilung	Bonn
Germany	DIK Deggendorf, Onkologische Ambulanz	Deggendorf
Germany	Universitätsklinikum Carl Gustav Carus an der TU Dresden, Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie	Dresden
Germany	Universitätsklinikum Erlangen, Chirurgische Klinik Zentrum für klinische Studien	Erlangen
Germany	Universitätsklinikum Frankfurt, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie,	Frankfurt
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	Universitätsklinikum Hamburg Eppendort, Zentrum für operative Medizin, Klinik und Poliklinik für Allgemein-, Viszeral- und Thoraxchirurgie	Hamburg
Germany	Medizinische Hochschule Hannover, Klinik für Gastroenterologie, Hepatologie und Endokrinologie	Hannover
Germany	Universitätsklinikum Heidelberg, Abteilung für Allgemein-, Viszeral- und Transplantationschirurgie und Nationales Zentrum für Tumorerkrankungen, Medizinische Onkologie	Heidelberg
Germany	Universitätsklinikum des Saarlandes, Klinik für Innere Medizin II und Klinik für Allgemeine Viszeral Gefäß und Kinderchirurgie	Homburg/Saar
Germany	Univeristätsklinikum Jena	Jena
Germany	UKSH Campus Kiel, Medizinische Klinik II	Kiel
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	Universitätsmedizin der Johannes Gutenberg-Universität Mainz, I. medizinische Klinik, Klinik für Allgemein-, Viszeral- und Transplantationschirurgie	Mainz
Germany	Universitätsklinikum Mannheim, II. medizinische Klinik, Klinik für Gastroenterologie, Hepatologie, Infektiologie und Ernährungsmedizin	Mannheim
Germany	Universitätsklinikum Marburg, Klinik für Innere Medizin, Gastroenterologie, Stoffwechsel und Endokrinologie	Marburg
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	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 Ulm, Klinik für Innere Medizin I Gastroenterologie-Endokrinologie-, Nephrologie-, Ernährung und Stoffwechselkrankheiten	Ulm
Germany	Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II Zentrum für Innere Medizin	Würzburg
Sweden	Centralsjukhuset	Karlstad
Sweden	Universitetssjukhuset	Linköping
Sweden	Skånes universitetssjukhus	Lund
Sweden	Norrlands universitetssjukhus	Umeå
Sweden	Akademiska sjukhuset	Uppsala

Sponsors (6)

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

Countries where clinical trial is conducted

Germany,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall survival	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.	76 months
Secondary	Metastasis free survival	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.	76 months
Secondary	Overall survival from recurrence	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.	76 months
Secondary	Quality of life (QoL EORTC QLQ-C-30)	QoL will be assessed by the EORTC QLQ-C30 questionnaire in its most current version every three months starting from V1.	76 months
Secondary	Safety: (serious) adverse events and Grade 3 and 4 toxicities according to NCI-CTC v.5.0.	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.	47 months