Nordic Pancreatic Cancer Trial (NorPACT) - 1

Study Overview
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Brief Summary
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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

Detailed Description
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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).

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: 5-FU
* Drug: Oxaliplatine
* Drug: Irinotecan
* Procedure: Pancreatic surgery
* Drug: 5-FU
* Drug: Oxaliplatine
* Drug: Irinotecan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Surgery and then postoperative adjuvant chemotherapy<br>Surgery and then postoperative adjuvant chemotherapy | Procedure: Pancreatic surgery<br>* All patients<br>Drug: 5-FU<br>* Adjuvant treatment<br>Drug: Oxaliplatine<br>* Adjuvant treatment<br>Drug: Irinotecan<br>* Adjuvant treatment<br>|
| Experimental: Neoadjuvant chemotherapy, surgery, adjuvant chemotherapy<br>Neoadjuvant chemotherapy, surgery, adjuvant chemotherapy | Drug: 5-FU<br>* Neoadjuvant treatment<br>Drug: Oxaliplatine<br>* Neoadjuvant treatment<br>Drug: Irinotecan<br>* Neoadjuvant treatment<br>Procedure: Pancreatic surgery<br>* All patients<br>Drug: 5-FU<br>* Adjuvant treatment<br>Drug: Oxaliplatine<br>* Adjuvant treatment<br>Drug: Irinotecan<br>* Adjuvant treatment<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant treatment