Chemotherapy And Surgical Resection In Patients With Hepatic Oligometastatic Adenocarcinoma Of The Pancreas

Study Overview

Chemotherapy and Surgical Resection in Patients With Hepatic Oligometastatic Adenocarcinoma of the Pancreas

This is an interventional, open-label, non-randomised, multicentre, single-arm phase II clinical trial. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant combination chemotherapy (liposomal irinotecan, oxaliplatin, 5-fluouracil, folinic acid (NAPOX)) in cycles of 14 days. Patients with tumour response or stable disease and a resectable primary tumour after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumour and hepatic metastases, if feasible; these patients may receive 4 more cycles of neoadjuvant chemotherapy 2-4 weeks after the explorative laparotomy if the surgeon rated the primary tumour as non-resectable during the explorative laparotomy.

This is an interventional, open-label, non-randomised, multicentre, single-arm phase II clinical trial. Eligible patients with hepatic oligometastatic adenocarcinoma of the pancreas will receive neoadjuvant NAPOX chemotherapy in cycles of 14 days. In patients with progressive disease during or after the first 4 cycles, neoadjuvant chemotherapy will be permanently discontinued. Patients with tumour response or stable disease after the first 4 cycles according to RECIST v1.1 but a non-resectable primary tumour according to the evaluation of an interdisciplinary tumour board will receive 4 more cycles of neoadjuvant chemotherapy. Patients with tumour response or stable disease and a resectable primary tumour after the first 4 cycles will undergo explorative laparotomy and synchronous resection of the tumour and hepatic metastases, if feasible; these patients may receive 4 more cycles of neoadjuvant chemotherapy 2-4 weeks after the explorative laparotomy if the surgeon rated the primary tumour as non-resectable during the explorative laparotomy. All patients who receive a total of 8 cycles and who then have tumour response or stable disease according to RECIST v1.1 will undergo exploratory laparotomy surgery and synchronous resection of the tumour and hepatic metastases, if feasible according to the surgeon, 2-6 weeks after the last investigational medicinal product (IMP) treatment. The primary endpoint of the clinical trial is overall survival of patients with an R0/R1 resection after neoadjuvant chemotherapy. The IMP treatment will be discontinued if tumour progression or inacceptable toxicity occurs or other termination criteria apply. Adjuvant treatment will not be part of the trial treatment and may be given at the investigator's discretion in accordance with the Onkopedia guideline for pancreatic cancer. Tumour, stool and blood samples will be collected before start and during the clinical trial for translational research if the patient gives his/her consent to participating in the translational research programme.

Pancreatic Cancer
Metastasis
Surgery
Oligometastatic Disease

DRUG: nal-irinotecan (nal-iri) (Onyvide), oxaliplatin (ox), 5-fluouracil (5-FU), folinic acid (FA)

Uni-Koeln-4067
2019-002734-37 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )
20-1544-AMG (OTHER Identifier) (OTHER: Local Ethics Committee University of Cologne)

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 2020-10-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2024-01-09
First Submitted that Met QC Criteria 2020-11-04	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2024-01-12
First Posted (ACTUAL) 2020-11-05	Results First Posted N/A	Last Verified 2024-01

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: NAPOX chemotherapy NAPOX chemotherapy in 14-day cycles with the four IMPs given intravenously in the following order: nal-irinotecan, oxaliplatin, folinic acid and 5-fluouracil.	DRUG: nal-irinotecan (nal-iri) (Onyvide), oxaliplatin (ox), 5-fluouracil (5-FU), folinic acid (FA) preoperative chemotherapy

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: NAPOX chemotherapy

NAPOX chemotherapy in 14-day cycles with the four IMPs given intravenously in the following order: nal-irinotecan, oxaliplatin, folinic acid and 5-fluouracil.

DRUG: nal-irinotecan (nal-iri) (Onyvide), oxaliplatin (ox), 5-fluouracil (5-FU), folinic acid (FA)

preoperative chemotherapy

Primary Outcome Measures	Measure Description	Time Frame
Overall survival after R0/R1 resection (OS-res)	OS for patient after macroscopic tumor resection	max 24 months follow-up

Secondary Outcome Measures	Measure Description	Time Frame
R0/R1 resection rate after neoadjuvant chemotherapy	Fraction of patients that undergo macroscopically complete tumor resection (No and %)	direct after operation
Overall survival (OS)	time from study inclusion until death (months)	max 24 months follow-up
Progression-free survival (PFS) after R0/R1 resection according to RECIST v1.1	time from study inclusion until tumor progress/recurrence (months)	max 24 months follow-up
Type, frequency and severity of adverse events (AE) with severity (SAE) according to NCI CTCAE version 5.0	Number and fraction of AE/SAEs (No and %)	direct after IMP administration up to 3 months after completion of study
HR-QoL according to EORTC QLQ-C30	Quality of Life according to the EORTC QLQ-C30 questionaire (scale 0 (poor) - 7 (excellent)	90 days after operation
Quality of life (QoL) according to EORTC QLQ-PAN-26	Quality of Life according to the EORTC QLQ-PAN26 questionaire (scale 0 (poor) - 7 (excellent)	90 days after operation
QoL-adjusted OS	time from study inclusion until death (months) adjusted to quality of life	max 24 months follow-up

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: Florian Gebauer, MD

Phone Number: +492028961563

Email: florian.gebauer@helios-gesundheit.de

Study Contact Backup

Name: Dirk Waldschmidt, MD

Phone Number:

Email: dirk.waldschmidt@uk-koeln.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:

Calculated creatinine clearance ≥60 mL/min
Total bilirubin ≤2 mg/dL; patients with biliary stent may be included if bilirubin level decreased to ≤2 mg/dL after stent insertion
alanin-aminotransferase and aspartat-aminotransferase (ALT and AST) ≤5 × upper limit of normal (ULN)
Absolute neutrophil count (ANC) ≥1.5 × 109/L
Thrombocytes ≥100 × 109/L
Haemoglobin ≥9 g/dL
activated partial thromboplastin time (aPTT) ≤1.5 × ULN and Quick value ≥70% 5. Patients ≥18 years at the time of signing the informed consent 6. Females of childbearing potential (FCBPs) must agree to use highly effective contraceptive measures (Pearl index <1) or practice true abstinence from any heterosexual intercourse for the duration of treatment and for at least 1 month after the last IMP administration (true abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient). A woman will be considered as being of childbearing potential unless she is at least 50 years old and, moreover, has gone through menopause for at least 2 years or has been surgically sterilised. 7. Males must agree to use condoms or practice true abstinence from any heterosexual intercourse for the duration of IMP treatment and at least 6 months after the last IMP administration (true abstinence is acceptable if this is in line with the patient's preferred and usual lifestyle). Male patients must furthermore refrain from donating sperm during the clinical trial until at least 6 months after the last IMP administration. 8. Patient's written informed consent prior to any trial-specific procedure 9. Patient's legal capacity to consent to participation in the clinical trial

Collaborators and Investigators

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

Servier

Investigators

PRINCIPAL_INVESTIGATOR: Florian Gebauer, MD, University of Witten/Herdecke

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

Gebauer F, Damanakis AI, Popp F, Quaas A, Kutting F, Lutz K, Held S, Deuss B, Goser T, Waldschmidt D, Bruns C. Study protocol of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with Oxaliplatin and 5-fluorouracil/Folinic acid followed by curative surgical resection in patients with hepatic Oligometastatic adenocarcinoma of the pancreas (HOLIPANC). BMC Cancer. 2021 Nov 18;21(1):1239. doi: 10.1186/s12885-021-08966-3.

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Clinical Trial Record