Nordic Pancreatic Cancer Trial (NorPACT) - 1

Nordic Multicentre Un-blinded Phase II Randomized Controlled Trial (RCT) Evaluating the Additional Efficacy of Adding Chemotherapy Prior to Resection of a Pancreatic Head Malignancy to Avoid Early Mortality in Those Ultimately Resected

This study evaluate the additional effect of adding chemotherapy prior to resection of a pancreatic head malignancy. The patients will be randomized into two groups; surgery first (control group) and neoadjuvant chemotherapy (intervention). Primary endpoint is overall survival after resection

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: 5-FU; Drug: Oxaliplatine; Drug: Irinotecan; Procedure: Pancreatic surgery; Drug: 5-FU; Drug: Oxaliplatine; Drug: Irinotecan

Detailed Description

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Europe and the United States. Surgical resection remains the only potentially curative treatment. However, the median survival of patients undergoing pancreatic resection alone is 16-23 months. The administration of adjuvant chemotherapy leads to an improvement in overall survival. Thus, completion of multimodality treatment (MMT) is the ideal goal and standard of care for treatment of pancreatic ductal adenocarcinoma (PDAC).

Currently, the surgery-first (SF) strategy is the most universally accepted approach to resectable PDAC (and is the standard of care in Norway), but the optimal sequence of surgery and chemotherapy remains unclear.

The purpose of this study is to further investigate the additional efficacy of neoadjuvant chemotherapy to the standard treatment for resectable cancer of the pancreatic head (surgery followed by adjuvant chemotherapy).

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Odense, Denmark
    • Per Pfeiffer
• Finland
  • Helsinki, Finland, 00029
    • Ville Sallinen
• Norway
  • Bergen, Norway, 5021
    • Haukeland University Hospital
  • Oslo, Norway, N- 0424
    • Oslo University Hospital
  • Stavanger, Norway, 4011
    • Stavanger University Hospital
  • Stavanger, Norway, 9038
    • Tromsø University Hospital
  • Trondheim, Norway, 7030
    • St. Olav University Hospital
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
  • Huddinge, Sweden, 14157
    • Karolinska University Hospital
  • Linköping, Sweden, 58185
    • Linkoping University Hospital
  • Lund, Sweden
    • Skåne University Hospital
  • Umeå, Sweden, 90737
    • University Hospital of Umeå
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Resectable adenocarcinoma of the pancreatic head
• T1-3, Nx, M0 (UICC 7th version, 2010)
• Cytologic or histologic confirmation of adenocarcinoma
• Age > 18 year and considered fit for major surgery
• Written informed consent
• Considered able to receive the study specific chemotherapy

Exclusion Criteria:

• Co-morbidity precluding pancreaticoduodenectomy
• Chronic neuropathy ≥ grade 2
• WHO performance score > 2 • Granulocyte count < 1500 per cubic millimetre
• Platelet count < 100 000 per cubic millimeter
• Serum creatinine > 1.5 UNL (upper limit normal range)
• Albumin < 2,5 g/dl
• Female patients in child bearing age not using adequate contraception, pregnant or lactating women • Mental or organic disorders which could interfere with informed consent or treatments
• Other malignancy within the past 5 years, except non-melanomatous skin or non-invasive cervical cancer
• Percutaneous tumor biopsy
• Any reason why, in the opinion of the investigator, the patient should not participate
• Pregnancy
• Breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Surgery and then postoperative adjuvant chemotherapy	Drug: 5-FU; Neoadjuvant treatment; Drug: Oxaliplatine; Neoadjuvant treatment; Drug: Irinotecan; Neoadjuvant treatment; Procedure: Pancreatic surgery; All patients; Drug: 5-FU; Adjuvant treatment; Drug: Oxaliplatine; Adjuvant treatment; Drug: Irinotecan; Adjuvant treatment
EXPERIMENTAL: Neoadjuvant chemotherapy, surgery, adjuvant chemotherapy	Drug: 5-FU; Neoadjuvant treatment; Drug: Oxaliplatine; Neoadjuvant treatment; Drug: Irinotecan; Neoadjuvant treatment; Procedure: Pancreatic surgery; All patients; Drug: 5-FU; Adjuvant treatment; Drug: Oxaliplatine; Adjuvant treatment; Drug: Irinotecan; Adjuvant treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival 18 month after randomization	Overall survival at 18 months after date of randomization (intention to treat)	18 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall mortality at one year following commencement of allocated treatment.	Overall mortality at one year following commencement of allocated treatment (NT or SF) for those who ultimately undergo resection	1 year
Disease-free survival	Patient will come to regular after surgery for follow-up visits regarding their disease.	until 5 years after surgery
Histopathological response	The histopathological response of the tumor to the neoadjuvant treatment will be assessed by established scores (R0 resection and (y)pN0 disease)	Arm 1: Baseline and Arm 2; 4 weeks after baseline
Complication rate after surgery	Complication rate after surgery as measured by Dindo-Clavien/ISPGS classification systems	30 and 90 days
Feasibility of neoadjuvant and adjuvant chemotherapy	The feasibility of neo-adjuvant and adjuvant chemotherapy measured by common Terminology Criteria for Adverse Events, grade 3-5, dose reduction and dose delay	Baseline
Health related Quality of Life	Data of quality of life will be assessed by the questionnaires EORTC QLQ-30	until 5 years after surgery
Health economics	Data of quality of life will be assessed by the questionnaires EQ-5D	until 5 years after surgery

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University Hospital of North Norway; Helse Stavanger HF; Haukeland University Hospital; St. Olavs Hospital
• Investigators: Principal Investigator: Knut Jorgen Labori, MD PhD, Oslo University Hospital

Publications and helpful links

General Publications

• Labori KJ, Lassen K, Hoem D, Gronbech JE, Soreide JA, Mortensen K, Smaaland R, Sorbye H, Verbeke C, Dueland S. Neoadjuvant chemotherapy versus surgery first for resectable pancreatic cancer (Norwegian Pancreatic Cancer Trial - 1 (NorPACT-1)) - study protocol for a national multicentre randomized controlled trial. BMC Surg. 2017 Aug 25;17(1):94. doi: 10.1186/s12893-017-0291-1.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (ACTUAL): December 22, 2022
• Study Completion (ANTICIPATED): April 30, 2026

Study Registration Dates

• First Submitted: September 14, 2016
• First Submitted That Met QC Criteria: September 28, 2016
• First Posted (ESTIMATE): September 29, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Neoadjuvant treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Fluorouracil; Oxaliplatin; Irinotecan
• Other Study ID Numbers: NorPACT-1; 2015-001635-21 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO