Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Nutritional and Metabolic Diseases

Rare Diseases

Pancreatic Neoplasms

Malnutrition

Exocrine Pancreatic Insufficiency

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Nutrition Disorders

Pancreatic Cancer

Patients, fulfilled inclusion criteria with Mini-Nutritional Assessment score of 24-30 points.

Patients, fulfilled inclusion criteria with Mini-Nutritional Assessment score of fewer than 17 points.

Gabriele Capurso, MD, PhD

Enrique de Madaria, MD, PhD

Vasile Sandru, MD

Mariia Kiriukova, MD

Nikola Panic, MD

Maryana Bozhychko, MD

Daniel de la Iglesia Garcia, MD

Bartu Avci

Malnutrition and cachexia are common in patients with advanced pancreatic ductal adenocarcinoma (PDAC) and have a significant influence on the tolerance and response to treatments. If timely identified, malnourished PDAC patients could be treated to increase their capacity to complete the planned treatments and therefore, possibly, improve their efficacy.

The aim of the study is to assess the impact of nutritional status, pancreatic exocrine insufficiency (PEI), and other clinical factors on patient outcomes in patients with advanced PDAC.

The nutritional status will be determined by means of Mini-Nutritional Assessment score and laboratory blood tests. PEI will be defined as the presence of typical symptoms and/or reduced fecal elastase. Analysis: chemotherapy dosing over the first 12 weeks of therapy (i.e. percent of chemotherapy received in the first 12 weeks, as defined above) PAC-MAIN will provide insights on the role of malnutrition and PEI in outcomes of PDAC.

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.

Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer

Drug doses will be expressed in weight-based, body surface area (BSA)-based, Area Under the Curve (AUC) units or flat dose, according to standard dosing practice for a given drug or combination. For each drug in a regimen, the sum of the doses delivered during the first 12 weeks of therapy will be divided by the sum of the expected doses based on published standard schedule and dosing. The mean percent dose delivered of all drugs in a regimen will be reported as 'percent of standard chemotherapy dose delivered.' The investigators will use percent of standard chemotherapy dose delivered to estimate the overall relative dose delivered.

Similarly, the sum of the doses delivered during the first 12 weeks of therapy will be divided by the sum of the expected doses based on each patient's starting chemotherapy dose, and the mean percent dose delivered for all drugs in a regimen will be reported as 'percent of planned chemotherapy delivered.' The investigators will use percent of planned chemotherapy dose delivered to quantify further dose reductions from starting dose and as an indicator of overall toxicity.

The pancreatic cancer module is designed for patients at all disease stages undergoing surgical resection, palliative surgical intervention, endoscopic palliation or palliative chemotherapy (Fitzsimmons et al., 1999a,b). The module comprises 26 questions assessing pain, dietary changes, jaundice, altered bowel habit, emotional problems related to pancreatic cancer, and other symptoms (cachexia, indigestion, flatulence, dry mouth, taste changes). The answers range is the following: not at all - 1 point, a little - 2 points, quite a bit - 3 points, very much - 4 points. Minimum score is 26, maximum is 106. The higher total score represents the worse quality of life.

University of Santiago de Compostela

University Clinic Dr Dragisa Misovic-Dedinje

University of Belgrade

Hospital General Universitario de Alicante

Istanbul University

European Institute of Oncology

IRCCS San Raffaele

Bucharest Emergency Hospital

Moscow Clinical Scientific Center

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Diseases and Abnormalities at or Before Birth

Fibrosis

Cystic Fibrosis

Pancreatitis

Pancreatitis, Chronic

Lung Diseases

Respiratory Tract Diseases

Genetic Diseases, Inborn

Infant, Newborn, Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Gastrointestinal Agents

All Drugs and Chemicals

Pancrelipase

Pancreatin

Participants will receive daily dose of CREON.

CREON

ABBVIE INC.

Exocrine pancreatic insufficiency (EPI) is a condition where the pancreas does not have enough pancreatic enzymes to break down food. Some symptoms of EPI are frequent gas/bloating, unexplained stomach pains, frequent diarrhea, and foul-smelling, greasy stools. The purpose of this study is to see how effective CREON is for treating symptoms of EPI due to causes other than cystic fibrosis (CF), chronic pancreatitis (CP), pancreatectomy (PY), or pancreatic cancer (PC).

CREON (Pancrelipase) is an approved drug used to treat people who cannot digest food normally due to their pancreas not making enough enzymes. Adult participants with a diagnosis of EPI due to causes other than CF, CP, PY, or PC will be enrolled. Around 50 participants will be enrolled in approximately 20 sites in the United States.

Participants will receive oral CREON capsules with each meal and snack beginning at Day 1 for 27 weeks.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or a clinic. Participants will need to be confined for 2 separate periods of 6 to 8 days each to measure Co-efficient of Fat Absorption (during screening and after enrollment). The effect of the treatment will be checked by medical assessments, blood and stool tests, checking for side effects and completing questionnaires.

Study Of Effects Of Oral CREON Capsules In Adult Participants With Exocrine Pancreatic Insufficiency Not Due To Cystic Fibrosis, Chronic Pancreatitis, Pancreatectomy, Or Pancreatic Cancer

A Phase 4 Open-Label Single-Arm Study To Evaluate The Use Of CREON In Subjects With EPI Due To Etiologies Other Than Cystic Fibrosis, Chronic Pancreatitis, Pancreatectomy, Or Pancreatic Cancer

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

CFA is calculated as 100\*\[fat intake - stool fat\]/fat intake. Fat intake will be determined from fat content of food consumed on Days 3 to 5 in the confinement period. Stool fat will be determined from the fat content in the stool(s) collected between the two dye markers in the confinement period.

Change in GI symptoms is measured by AbbVie exocrine pancreatic insufficiency (EPI) symptom questionnaire. EPI symptom questionnaire is a 12-item patient-reported outcome (PRO) instrument that assesses EPI symptoms over the past 7 days.

Stool frequency per 24 hours will be recorded daily during the 2 confinement periods. The average stool frequency per 24 hours during confinement period 1 will be considered as baseline.

Stool consistency will be evaluated using the Bristol Stool Scale. The Bristol Stool chart is a medical aid designed to classify feces.

Change from Baseline in vitamin D will be assessed through clinical laboratory testing.

Change from Baseline in vitamin E will be assessed through clinical laboratory testing.

Change from Baseline in vitamin K will be assessed through clinical laboratory testing.

Change from Baseline in vitamin A will be assessed through clinical laboratory testing.

Change from Baseline in retinol-binding protein will be assessed through clinical laboratory testing.

Change from Baseline in albumin will be assessed through clinical laboratory testing.

Change from Baseline in prealbumin will be assessed through clinical laboratory testing.

Change from Baseline in transferrin will be assessed through clinical laboratory testing.

The mean change of weight from Baseline will be calculated.

BMI is a measure of body fat based on weight in relation to height.

Hip circumference is measured by placing the measuring tape around the maximum circumference of the buttocks.

Waist circumference is measured by placing a measuring tape on top of the hip bone and wrapping the tape around the waist.

GIQLI is a 36-item patient reported outcome (PRO) instrument used to assess GI-specific quality of life in participants with GI disorders, with response score ranging from 0 to 4 (0 being "all the time" and 4 being "never").

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer	NCT04112836	Pancreatic Canc... Exocrine Pancre... Metastatic Panc... Chemotherapy Malnutrition Locally Advance...		18 Years -	Moscow Clinical Scientific Center
Study Of Effects Of Oral CREON Capsules In Adult Participants With Exocrine Pancreatic Insufficiency Not Due To Cystic Fibrosis, Chronic Pancreatitis, Pancreatectomy, Or Pancreatic Cancer	NCT04315311	Exocrine Pancre...	CREON	18 Years -	AbbVie
Pancreatic Cancer Malnutrition and Pancreatic Exocrine Insufficiency in the Course of Chemotherapy in Unresectable Pancreatic Cancer	NCT04112836	Pancreatic Canc... Exocrine Pancre... Metastatic Panc... Chemotherapy Malnutrition Locally Advance...		18 Years -	Moscow Clinical Scientific Center

Spots Global Cancer Trial Database for exocrine pancreatic insufficiency