Investigators hypothesize that malnutrition has an adverse impact on the clinical course of
patients with advanced PDAC treated with chemotherapy.
Aims:
To investigate the association between the nutritional status and pancreatic exocrine
function and the clinical outcomes of patients with advanced PDAC.
Study design:
The PAncreatic Cancer MAlnutrition and exocrine pancreatic INsufficiency in the course of
chemotherapy in unresectable pancreatic cancer (PAC-MAIN) study is a non-profit,
international, multicentre, prospective, observational, cohort study evaluating the effect of
the nutritional status and pancreatic exocrine function on the main outcomes of patients with
advanced PDAC. The study will be carried out in Russia, Turkey, Serbia, Romania, Italy, and
Spain as a part of the Pancreas 2000 Educational Program. Pancreas 2000 is a post-graduate
educational program that prepares young gastroenterologists, surgeons, radiologists, and
other physicians for specialization in Pancreatology.
Patient-related:
sex, race, age at diagnosis
Mini-Nutritional Assessment (MNA) score
sarcopenia (measured with computed tomography (CT) fat free mass is reduced; i.e.
appendicular\L2 skeletal muscle mass index <7.2 kg/m2 (men) or <5.5 kg/m2 (women));
cachexia (weight loss (WL)>5% in last 6 months, or WL>2% if body mass index (BMI) <20
kg/m² or sarcopenia);
12-item functional assessment of anorexia/cachexia therapy anorexia/cachexia subscale
(FAACT-A/CS-12)
a biliary stent
a duodenal stent
total and direct bilirubin
ECOG status
European Organization for Research and Treatment of Cancer (EORTC) QLQ-PAN26 scale
Date of diagnosis, visit 1, visit 2 (3 months), and death/loss from follow up
Check up on survival at 6m
Tumor-related:
Tumor site documented by endoscopic ultrasound, CT, or magnetic resonance imaging (head,
body, or tail)
Stage according to the TNM classification
Vessels involved
Presence and site of metastatic disease
Ascites
CA-19-9
Response evaluation criteria in solid tumors (RECIST) (for visit 2)
Nutritional parameters:
Leucocytes (lymphocytes, neutrophils), neutrophil to lymphocytes ratio, erythrocytes,
hemoglobin, hematocrit, platelets
C-reactive protein, total protein, albumin, cholesterol, iron, transferrin, ferritin,
magnesium, zinc
International normalized ratio, activated partial thromboplastin time
Blood fasting glucose, glycated hemoglobin
Pancreatic function and treatment:
PEI, fecal elastase-1, pancreatic enzyme replacement therapy (PERT), date of starting
PERT, the dosage of daily taken PERT
Diabetes mellitus (DM), date of DM diagnosis, DM type, DM treatment
Treatment-related:
Planned chemotherapy protocol Dosages of chemotherapy planned (mg/m2)
Percent of standard chemotherapy dose delivered
Percent of planned chemotherapy delivered
Changes to the predefined schedule (dose reduction, schedule modifications, stop before
planned)
Date of treatment start and end
Adverse events (National Cancer Institute toxicity scale for visit 2)
Description of the intervention (schedule of visits):
Visit 1 (screening, within 1 month from initial diagnosis). Patients will be informed about
the study. Once patients agree with the inclusion in the study the investigators will
evaluate the inclusion and exclusion criteria. Those patients who meet all the inclusion
criteria and none of the exclusion criteria will be finally included in the study. In this
visit, patients, tumor-related variables, and general patients' features will be recorded,
and quality of life questionnaire will be administered. The researcher will record weight,
height, body mass index (BMI), unplanned WL % for the last 6 months.
Each patient's baseline nutrition status will be evaluated using the MNA scores prior to
starting chemotherapy. Patients will be classified as in the group with no nutritional risk,
at risk of malnutrition, or malnourished.
Nutritional parameters and pancreatic function will be evaluated through blood tests and a
fecal test.
Visit 2 (3 months after the first dose of planned chemotherapy). The researcher will record
in the case report form (CRF) the planned chemotherapy, schedule, doses, dose reduction, and
any adverse event. The same variables recorded at Visit 1 will be checked again.
Check up 3 (end of the study, 6 months). The researcher will record in the CRF the overall
survival and time until progression.
Medication of the study:
The study is of observational nature, so a pre-planned treatment is not considered. However,
the use of pancreatic enzyme replacement treatment will be recorded as well as data regarding
the employed chemotherapy regimen.
Power size calculation:
The expected percent of chemotherapy delivered in well-nourished patients was based on a
study that assessed the chemotherapy dose intensity in gastrointestinal malignancies included
pancreaticobiliary disease during the firsts 8 weeks after the start of the chemotherapy23.
Based on an expected percentage of chemotherapy delivered of 70% in well-nourished patients,
with a type I error of 0.05 and a type II error of 0.20, a sample size of 93 patients per
group will be required in case of a percentage difference of chemotherapy delivered of 20%
between well-nourished and malnourished, 163 patients per group in case of a difference of
15% between both groups and 356 patients per group in case of 10% of difference.
Discussion:
Given the sparse overall scientific data on the subject, the investigators have designed a
study that addresses the impact of patient's nutritional status and dietary intervention on
the clinical course of patients with advanced PDAC treated with chemotherapy and is aimed at
establishing whether it affects both tolerance and tumor response to medical therapy.
PAC-MAIN will be the first study specifically investigating whether the nutritional status
influences the possibility to complete planned chemotherapy in patients with advanced PDAC.