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

Study Overview

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

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).

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.

Pancreatic Ductal Adenocarcinoma

DRUG: Oxaliplatin
DRUG: Irinotecan
DRUG: Folinic acid
DRUG: 5-fluorouracil
DRUG: Gemcitabine
DRUG: Capecitabine

ESPAC-6
AIO-PAK-0121/ass (OTHER Identifier) (OTHER: AIO)
2020-004906-79 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-03-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-12-05
First Submitted that Met QC Criteria 2022-03-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-12-10
First Posted (ACTUAL) 2022-04-07	Results First Posted N/A	Last Verified 2024-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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	DRUG: Oxaliplatin 85 mg/m2 D1 over 2 hours every; 14 days, 12 cycles, 24 weeks 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 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 DRUG: 5-fluorouracil 2.4 g/m2 IV continuous infusion over 46 hours (1200 mg/m2/ day); every 14 days, 12 cycles, 24 weeks 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 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
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	DRUG: Oxaliplatin 85 mg/m2 D1 over 2 hours every; 14 days, 12 cycles, 24 weeks 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 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 DRUG: 5-fluorouracil 2.4 g/m2 IV continuous infusion over 46 hours (1200 mg/m2/ day); every 14 days, 12 cycles, 24 weeks 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 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

Participant Group/Arm

Intervention/Treatment

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

DRUG: Oxaliplatin

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

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

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

DRUG: 5-fluorouracil

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

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

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

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

DRUG: Oxaliplatin

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

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

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

DRUG: 5-fluorouracil

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

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

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

Primary Outcome Measures	Measure Description	Time Frame
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 Outcome Measures	Measure Description	Time Frame
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
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
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
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
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: John Neoptolemos, Prof. Dr.

Phone Number: 0049 6221 56-39020

Email: john.neoptolemos@med.uni-heidelberg.de

Study Contact Backup

Name: Claudia Pauligk, Dr.

Phone Number: 0049 69 6301 - 3906

Email: pauligk.claudia@ikf-khnw.de

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Molecular Health GmbH
German Cancer Research Center
Nationales Centrum für Tumorerkrankungen
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Institut für Medizinische Biometrie

Investigators

STUDY_DIRECTOR: John Neoptolemos, Prof. Dr., Universität Heidelberg

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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