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Clinical trials pancreatic diseases

Also our clinical research evolves around the pancreas and is fully embedded in our daily clinical routine at the gastroenterology wards and endoscopy units here at KUM. By recruiting patients to disease specific databases with biobanking and testing promising treatment approaches in clinical trials we hope to learn with and from our patients by offering them the best care available.

We are currently recruiting patients with acute and chronic pancreatitis as well as suspected or proven pancreatic cancer to ongoing clinical trials.



Mag-PEP: Pre-study protocol MagPEP: a multicentre randomized controlled trial of magnesium sulphate in the prevention of post-ERCP pancreatitis

PI Markus M. Lerch
Fluhr G. et al. BMC Gastroenterol. 2013 Jan 15;13:11

Picture: Mag PEPBACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In spite of continuing research, no pharmacologic agent capable of effectively reducing the incidence of ERCP-induced pancreatitis has found its way into clinical practise. A number of experimental studies suggest that intrapancreatic calcium concentrations play an important role in the initiation of intracellular protease activation, an initiating step in the course of acute pancreatitis. Magnesium can act as a calcium-antagonist and counteracts effects in calcium signalling. It can thereby attenuate the intracellular activation of proteolytic digestive enzymes in the pancreas and reduces the severity of experimental pancreatitis when administered either intravenously or as a food supplement.

METHODS:
We designed a randomized, double-blind, placebo-controlled phase III study to test whether the administration of intravenous magnesium sulphate before and after ERCP reduces the incidence and the severity of post-ERCP pancreatitis. A total of 1004 adult patients with a medical indication for ERCP are to be randomized to receive either 4930 mg magnesium sulphate (= 20 mmol magnesium) or placebo 60 min before and 6 hours after ERCP. The incidence of clinical post-ERCP pancreatitis, hyperlipasemia, pain levels, use of analgetics and length of hospital stay will be evaluated.

CONCLUSIONS:
If magnesium sulphate is found to be effective in preventing post-ERCP pancreatitis, this inexpensive agent with limited adverse effects could be used as a routine pharmacological prophylaxis.

Supplementary information for study participants on data protection: Ergänzende Informationen für Studienteilnehmer MagPEP zum Datenschutz



Double Blind, Randomised, Controlled Trial to Investigate the Efficacy of ANTOX(vers)1.2 and MGCT (Magnesiocard®) for the Treatment of Hereditary Pancreatitis and Idiopathic Chronic Pancreatitis

Figure: Treatment of Hereditary Pancreatitis and Idiopathic Chronic Pancreatitis

Supplementary information for study participants on data protection: Ergänzende Informationen für Studienteilnehmer zum Datenschutz



Development and validation of a Chronic Pancreatitis Prognosis Score (COPPS) to predict hospital admission in two independent cohorts

PI: Georg Beyer, MD, BSc; Julia Mayerle, MD

The clinical course of chronic pancreatitis is unpredictable and so far, no prediction model to assess the dynamic disease severity has been established.

Patients and Methods: We prospectively recruited 111 patients with chronic pancreatitis. Clinical, laboratory and imaging data were correlated to number of readmissions and in-hospital days over the next 12 months, and parameters showing best correlation were used for development of a three stage chronic pancreatitis prognosis score (COPPS). The predictive value was validated in 129 independent subjects identified from two prospective databases.

The median number of hospital admissions was 2.3 [95%CI 1.8-2.8] and 16.5 for hospital days [95%CI 12.7-20.2] for the development cohort and 10.9 for the validation cohort [95% CI 7.5-14.3] (p=0.08). Based on bivariate correlations, pain (numeric rating scale), HbA1c, CRP, BMI and thrombocyte count were used for development of COPPS. Median COPPS was 9.1 points (range 5 to 14) and it successfully discriminated stages of disease severity (low to high): A (5-6 points), B (7-9) and C (10-15). Pearson correlation showed significant correlation to hospital admissions (0.52; p<0.01) and number of hospital days (0.40; p<0.01) in the development cohort. This correlation was validated in the validation set (0.44; p<0.01). There was no correlation with the Cambridge classification.

We developed and validated a novel, easy to use dynamic multivariate score similar to the Child-Pugh-Score for cirrhosis. COPPS allowed objective monitoring of chronic pancreatitis regarding readmission to hospital as well as length of hospital stay.

Currently, we are recruiting in a multicenter and multinational prospective study to validate our newly developed tool.

https://www.dfrs.de/coppss/


Figure: COPPS



Prospective Study on a Plasma Metabolome Multimarker Panel MxP® PancreasScore for the Diagnosis of Pancreatic Cancer in Cohorts at Risk

Bundesmin BiFoThe World Health Organization advocates that for 30% of all cancers an early diagnosis determines whether the patient can be cured (www.who.int/cancer/en/index.html). PDAC is projected to be the third leading cause of cancer-related death by 2030 due its late diagnosis and slow progress in terms of available treatment options. An earlier diagnosis could increase the 5 year survival by as much as 30-40%. As the incidence of PDAC in subjects >50 years of age is 12/100 000, a potential surveillance would require at least two sieves to increase pretest probability, make the strategy cost-effective, and exclude PDAC in cohorts with significantly increased risk. The first sieve would select for well-defined groups with an increases PDAC risk, e.g. individuals from familial PDAC families (prevalence: 3/100 000), patients with CP (prevalence 50/100 000), or newly diagnosed onset of diabetes over the age of 50 years (prevalence 1.29/100). The second sieve would select for the metabolome signature MxP® PancreasScore identified by this consortium. It has previously been established that a new diagnostic assay for PDAC, in order to reduce health care expenditure and prolong patient survival, would have to perform with a minimum sensitivity of 88% at a specificity of 85% if the incidence is equal or above 0.71% as in newly diagnosed diabetics over the age of 50 years. The best established blood test for the diagnosis of PDAC is carbohydrate antigen 19-9 (CA19-9). Unfortunately, CA19-9 can also be elevated in patients with nonmalignant diseases. CA19-9 has been reported to discriminate between PDAC patients and healthy controls (sensitivity 80.3%, 95%CI 77.7-82.6; specificity 80.2%, 95%CI 78.0-82.3). By comparison, MxP® PancreasScore detected only 9% false positives compared to 23% for CA19-9 and identified an additional 15% of patients in whom the diagnosis of PDAC was missed when using CA19-9 alone. Thus MxP® PancreasScore exceeds the performance of CA19-9 and of a miRNA panel previously published.
Currently, we are recruiting to validate the assay in a prospective trial under the protocol below.


STUDY SYNOPSIS

PRINCIPAL INVESTIGATOR(S)

Julia Mayerle, Prof. Dr. med.

Medizinische Klinik und Poliklinik II

Klinikum der LMU München-Grosshadern
Anstalt des öffentlichen Rechts

Marchioninistr. 15
D-81377 München

Germany

Tel +49 (0) 89 4400-72390
Fax +49 (0) 89 4400-78887

Email: julia.mayerle@med.uni-muenchen.de

TITLE OF STUDY

Prospective Study on a Plasma Metabolome Multimarker Panel MxP® PancreasScore for the Diagnosis of Pancreatic Cancer in Cohorts at Risk

CONDITION

Pancreatic mass lesion of unknown aetiology in cohorts at increased risk for pancreatic ductal adenocarcinoma (PDAC)

OBJECTIVE(S)

Primary Aim: Confirmation of sensitivity of ≥88% at fixed specificity of 85% of MxP® PancreasScore for the detection of PDAC in a population at risk.

Secondary Aims: 1) Characterization of new onset of diabetes cohort (at >50 years of age) in terms of MxP®PancreasScore and clinical follow up 2) Diagnostic accuracy of the metabolome signature MxP®PancreasScore with regard to tumour stage and volume. 4) practical feasibility of testing for the metabolome signature in clinical routine (for detail see test-optimization) 5) follow-up of MxP®PancreasScore false negative results to understand causes of incorrect diagnosis (e.g. tumour burden, pre-analytics or analytics) 5) specificity for malignant disease of the pancreas other than PDAC 6) changes in metabolic signature over time of progression or treatment

STUDY DESIGN

Prospective, consecutive, multi-centre, multi-disciplinary, investigator blinded metabolite signature screening study

VALIDATION CRITERIA

For the primary aim the final diagnosis of PDAC will be confirmed by histopathology (either resection specimen, pancreatic fine needle aspiration or biopsy of metastasis) or ruled out in patients with likely benign disease by minimum clinical follow-up of 24 months (twice the median survival of locally advanced PDAC). For secondary aim  patients with newly diagnosed diabetes mellitus over age 50 will be followed for 36 month to exclude PDAC.

KEY INCLUSION AND EXCLUSION CRITERIA

Key inclusion criteria:

  • solid pancreatic mass lesion on imaging (abdominal CT) requiring further diagnostic work-up (including patients with newly diagnosed diabetes (DM), familial PDAC families and chronic pancreatitis (CP); n =1375) OR
  • new onset of diabetes over the age of 50 years (n= 200)

Key exclusion criteria:

  • Inability to give informed consent
  • Current pregnancy
  • Conditions precluding surgery, biopsy or clinical follow-up

OUTCOME MEASURE(S)

Primary efficacy endpoint: Diagnosis of PDAC with high specificity

Key secondary exploratory endpoint(s): Confirmed/excluded cancerous or precancerous lesions of the pancreas by imaging, histology or a minimum of 24 months follow up. Effect of tumour subtype, grading or staging (TNM), medication, dyslipidemia, or associated diseases on MxP®PancreasScore. Changes in MxP®PancreasScore under treatment and during progression.

Assessment of safety: Standardized follow up of all patients recruited, reporting of AE and SAE. Determination of MxP®PancreasScore false positive and false negative rate based on clinical endpoints.

 STATISTICAL ANALYSIS

Efficacy / test accuracy:

Observed sensitivity of ≥ 88% at fixed specificity of 85%, power of 80%, resulting in an negative predictive value (NPV) >99.9%, area under the curve (AUC) of >0.95 in a cohort with PDAC prevalence of between 0.85% (DM) and 20% (focal pancreas lesion) employing the previously established MxP®PancreasScore signature.

Safety: Investigators will be blinded to MxP®PancreasScore test result and result will not be used for clinical decision making.

Secondary endpoints: Observed false positive rate ≤ 20% with a power of 80%

Significantly (p<0.05) better performance (AUC) in a cohort with solid pancreatic mass lesion on imaging when compared to CA19.9*

SAMPLE SIZE

To be assessed for eligibility: META-PAC-1: n = 1500 (focal lesion) and n=3125 (HbA1c screening for diabetes)

To be allocated to study: META-PAC1: n = 1375; n= 250 for new onset DM (HbA1c> 6.5 %). 10% drop-out due to pre-analytical, analytical or follow-up issues.

To be analysed: META-PAC-1: n = 1250 (Focal lesion); n=200 (HbA1c> 6.5 %); STARD diagram below

STUDY DURATION

First patient in to last patient out (months): 42 months

Duration of the entire study (months): 48 months

Recruitment period (months): 18 months


In collaboration with: http://www.metanomics-health.com/en/about-us.html