609 – Results from a Multicenter, Phase Ii, Open-Label, Nonrandomized Study of Ms1819 Spray Dried, a Recombinant Lipase for the Treatment of Exocrine Pancreatic Insufficiency in Patients with Chronic Pancreatitis

BackgroundAngiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).MethodsThis is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.ResultsAt data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.ConclusionsThe combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.AcknowledgementsFunding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb CompanyTrial RegistrationNCT02834013Ethics ApprovalThis study was approved by the NCI CIRB.

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229TiP A single arm, open-label, multicenter, phase II trial of oxaliplatin plus capecitabine (XELOX) in the perioperative treatment of locally advanced gastric adenocarcinoma in combination with D2 gastrectomy (NEO-CLASSIC)

Annals of Oncology ◽

10.1093/annonc/mdv523.90 ◽

2015 ◽

Vol 26 ◽

pp. ix42

Author(s):

T. Liu ◽

Y. Yu ◽

Y. Sun ◽

M. Yan ◽

H. Cao ◽

...

Keyword(s):

Gastric Adenocarcinoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Locally Advanced ◽

Open Label ◽

Perioperative Treatment ◽

D2 Gastrectomy ◽

Multicenter Phase ◽

Advanced Gastric Adenocarcinoma

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Early chronic pancreatitis: is a clinical diagnosis possible?

Herald of Pancreatic Club ◽

10.33149/vkp.2019.03.03 ◽

2019 ◽

Vol 44 (3) ◽

pp. 33-41

Author(s):

N. B. Gubergrits ◽

N. V. Byelyayeva ◽

A. Ye. Klochkov ◽

G. M. Lukashevich ◽

V. S. Rachmetova

Keyword(s):

Chronic Pancreatitis ◽

Diagnostic Criteria ◽

Pancreatic Insufficiency ◽

Exocrine Pancreatic Insufficiency ◽

Diagnostic Methods ◽

Test Results ◽

International Consensus ◽

Financial Costs ◽

Increased Risk ◽

Antifibrotic Drugs

A “fatal chain” in pancreatology is discussed in the present article; peculiar attention is paid to an early chronic pancreatitis (CP), being one of the little-studied “links” in this range and corresponding to the latent period of CP(persistence of inflammation with the presence of biomarkers of CP, which does not meet the diagnostic criteria of proven or late CP, as well as the appearance of signs of exocrine pancreatic insufficiency in the form of reduced functional test results to 70% of normal). Features of the different stages of the pancreatic diseases’ course are presented, substantiatinganeed for a practical identification of the “early CP” diagnosis: "for" - the possibility of timely diagnosis, the identification of patients with an increased risk of prostate cancer; "against": the lack of specific antifibrotic, anti-inflammatory therapy, an increase in financial costs, no impact on the clinical outcome.Advantages and disadvantages of using the “early CP” diagnosis in practice are considered. The authors cite the provisions of the International Consensus on early CP, and list the current diagnostic criteria for this diseaseelaborated by the Japanese Pancreas Society. Advantages and disadvantagesof the instrumental and laboratory diagnostic methods are analyzed, including probable early CP biomarkers (interleukin-8, prostaglandin E2). The most suitable therapeutic tactics for management of patients with early CP are presented, including correction of the exocrine and endocrinepancreatic function, as well as the use of antifibrotic drugs.

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Diagnosis and treatment of diabetes mellitus in chronic pancreatitis

Herald of Pancreatic Club ◽

10.33149/vkp.2017.04.02 ◽

2017 ◽

Vol 38 (4) ◽

pp. 15-21

Author(s):

N. Ewald ◽

P. D. Hardt

Keyword(s):

Diabetes Mellitus ◽

Chronic Pancreatitis ◽

Medical Therapy ◽

Pancreatic Insufficiency ◽

Clinical Importance ◽

Underlying Disease ◽

Exocrine Pancreatic Insufficiency ◽

Develop Type ◽

Fat Hydrolysis ◽

Type 3

Diabetes secondary to pancreatic diseases is commonly referred to as pancreatogenic diabetes or type 3c diabetes mellitus. It is a clinically relevant condition with a prevalence of 5-10% among all diabetic subjects in Western populations. In nearly 80% of all type 3c diabetes mellitus cases, chronic pancreatitis seems to be the underlying disease. The prevalence and clinical importance of diabetes secondary to chronic pancreatitis has certainly been underestimated and underappreciated so far. In contrast to the management of type 1 or type 2 diabetes mellitus, the endocrinopathy in type 3c is very complex. The course of the disease is complicated by additional present comorbidities such as maldigestion and concomitant qualitative malnutrition. General awareness that patients with known and/or clinically overt chronic pancreatitis will develop type 3c diabetes mellitus (up to 90% of all cases) is rather good. However, in a patient first presenting with diabetes mellitus, chronic pancreatitis as a potential causative condition is seldom considered. Thus many patients are misdiagnosed. The failure to correctly diagnose type 3 diabetes mellitus leads to a failure to implement an appropriate medical therapy. In patients with type 3c diabetes mellitus treating exocrine pancreatic insufficiency, preventing or treating a lack of fat-soluble vitamins (especially vitamin D) and restoring impaired fat hydrolysis and incretin secretion are key-features of medical therapy.

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Los criterios de Rosemont en ultrasonografía endoscópica: ¿son predictores de insuficiencia pancreática exocrina?

Acta gastroenterológica latinoamericana ◽

10.52787/qwpo5827 ◽

2021 ◽

Vol 51 (2) ◽

Author(s):

Marianela Arramón ◽

Agustina Redondo ◽

Pablo Cura ◽

Fernando Baldoni ◽

Ana Brizio ◽

...

Keyword(s):

Chronic Pancreatitis ◽

Endoscopic Ultrasonography ◽

Pancreatic Insufficiency ◽

Descriptive Study ◽

Exocrine Pancreatic Insufficiency ◽

Diagnostic Methods ◽

Fat Quantification ◽

Morphologic Characteristics ◽

Morphologic Changes

Endoscopic ultrasonography is the method of choice for detection of morphologic changes related to chronic pancreatitis. There are criteria, in the literature, that evaluate morphologic changes by endoscopic ultrasonography suggestive of chronic pancreatitis. The most widely used are the Rosemont criteria. Currently, the most effective diagnostic methods for exocrine pancreatic insufficiency are fat quantification (disused) and the 13C-mixed triglyceride breath test, not available in our country. However, the probability of diagnosis of pancreatic insufficiency can be estimated over the base of symptoms, malnutrition parameters, faecal elastase and signs of chronic pancreatitis in images. The aim of this study was to determine the correlation, probability and severity of exocrine pancreatic insufficiency, according to Rosemont criteria, in patients with chronic pancreatitis. A retrospective descriptive study was performed. Data were collected from patients between April of 2017 and April of 2018. The data gathered was based on pancreatic morphologic characteristics according to Rosemont criteria and related to the diagnosis of exocrine pancreatic insufficiency diagnosis based on the levels of stool elastase. Twenty one patients with chronic pancreatitis were included. The presence of hyperechogenic foci > 2 mm with posterior acoustic shadowing was associated with the presence of severe exocrine pancreatic insufficiency (p < 0.001). In our study, the association between parenchymal morphologic findings of chronic pancreatitis was significant in predicting exocrine pancreatic insufficiency. The role of endoscopic ultrasonography in predicting functional compromise in patients with chronic pancreatitis is promising.

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