Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Rare Diseases

Pancreatic Neoplasms

Adenocarcinoma

Pancreatitis

Pancreatitis, Chronic

Genetic Diseases, Inborn

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Diseases

Pancreatic Diseases

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Pancreatic Cancer

Anti-Infective Agents

All Drugs and Chemicals

Carbamide Peroxide

Bilirubin

Chronic pancreatitis, due to cystic fibrosis

Persons with a confirmed diagnosis of Peutz-Jeghers syndrome (STK11 mutation) or familial melanoma syndrome (CDKN2A mutation), hereditary pancreatitis (PRSS1 mutation)

Persons with a confirmed diagnosis of hereditary syndromes and at the same time with the condition of at least one relative of the first or second degree with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis; i.e. Lynch syndrome (mut: MLH1, MSH2, MSH6 a PMS2, EPCAM), HBOC (mut: BRCA1, BRCA2, PALB2, ATM), familial adenomatous polyposis (mut: APC), Li-Fraumeni syndrome (mut: TP53)

Persons with positive family anamnesis of pancreatic ductal adenocarcinoma without proven hereditary syndrome

endoscopic ultrasonography - frequency defined by arm

endoscopic ultrasonography

magnetic resonance - frequency defined by arm

magnetic resonance

hematology, biochemistry, Na+, K+, Cl-, Ca2+, bilirubin, ALT, AST, GGT, ALP, lactate dehydrogenase, creatinine, urea, fasting glycemia, HbA1c, alpha-amylase, LPS, albumin, total protein, CA19-9, CEA

laboratory examination

Martina Lojova, Ph.D.

Dita Kozakova, Ing.

Petr Karasek, MD

Jana Halamkova, MD

Helena Coupkova, MD

Anna Ondrackova, MD

Marketa Palacova, MD

Radim Nemecek, MD

Lumir Kunovsky, MD

Jan Trna, MD

Lenka Foretova, MD

Zdenka Cermakova, MD

Jan Kristek, MD

Roman Hrstka, Ph.D.

Pancreatic cancer is one of the diseases with the worst prognosis, which is mainly due to the initial asymptomatic prognosis. Unfortunately, the incidence of this disease in the Czech Republic is still increasing. In a certain proportion of patients, it is possible to predict the disease, e.g. due to family burdens. Regular follow-up of such individuals is the subject of the SCREPAN study: "Pancreatic Cancer Screening in High-Risk Persons".

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the worst prognosis. Mortality in this disease is almost equal to the incidence. In the Czech Republic, the incidence of this cancer has an upward trend, in 2017, 21.2 new cases per 100,000 people were reported, which represents a more than double increase compared to the data from the 1970s.

Pancreatic cancer is associated with an extremely poor prognosis for several reasons. It is usually diagnosed at an advanced stage, which is often due to the asymptomatic course of the disease or non-specific symptoms, the lack of sensitive and specific tumor markers, and difficult diagnosis by imaging methods in the early stages. Five-year survival, regardless of clinical stage, is between 7-9%.

Resectable disease is diagnosed in only 10% of patients, in which the 5-year survival rate is 37 %, locally advanced unresectable disease is detected in about 30 % of patients with a 5-year survival of 12 %, and metastatic disease is found in about 60 % of patients, with a 5-year survival rate of only around 3 %.

The poor prognosis of this disease is also due to the limited possibilities of screening and curative intervention for a short "lead time" in rapidly metastatic disease.

Pancreatic cancer screening is not suitable for the non-selected population. On the contrary, it is important for individuals with a high risk of developing this disease. In these subjects, early diagnosis during screening demonstrated a higher number of curative resections and longer survival.

Pancreatic Cancer Screening in a Population at High Risk

Number of participants (in risk population) with newly diagnosed pancreatic cancer

Comparison of magnetic resonance versus endoscopic ultrasonography yield

Comparison of magnetic resonance versus endoscopic ultrasonography cost effectiveness

KRAS mutation status defined by number of positive droplets on drop digital PCR using material from liquid biopsy

Masaryk University

Masaryk Memorial Cancer Institute

Blood and Lymph Conditions

Immune System Diseases

Behaviors and Mental Disorders

Lymphoma

Disease Progression

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Quality of Life

Lymphosarcoma

Primary Central Nervous System Lymphoma

Antineoplastic Agents

Analgesics

Central Nervous System Depressants

Antibodies

Antibodies, Monoclonal

Cytarabine

Morphine

Immunoglobulins

Fotemustine

To observe the efficacy and safety of a new generation of BTK inhibitor abutinib combined with PD-1 and formustine in the treatment of newly-treated patients with primary central nervous system lymphoma (PCNSL)

The study adopts the "3+3" design,The dose planned to be explored is the daily oral dose of the BTK inhibitor abutinib, which is 100 mg, 150 mg and 200 mg, respectively.Orelabrutinib continues to be taken orally until the tumor is relieved for 3 months; PD-1 monoclonal antibody is used by intravenous drip, 21 days as a treatment cycle, and a total of 1 year of observation; formustine is used by intravenous drip for 21 days It is a treatment cycle, a total of 6 cycles of observation; after 2 cycles, the efficacy is evaluated, and adverse reactions are recorded. At the same time, MTX 12mg+Ara-C 50mg+Dex 5mg was injected into the CSF cytology-positive sheath, and intrathecal injection once per treatment cycle, a total of 6 times.

the dose-escalation phase

Mingzhi zhang, Pro.Dr.

Mingzhi Zhang, Doctor

Mingzhi zhang

To observe the efficacy and safety of a new generation of BTK inhibitor Orelabrutinib combined with PD-1 and fotemustine in the treatment of patients with primary central nervous system lymphoma (PCNSL).

This study includes a dose escalation phase and an extended treatment phase . The dose-escalation phase： Primary study endpoint: Safety endpoint: including dose-limiting toxicity (DLT), adverse events, ECOG performance score, laboratory tests, vital signs, physical examination .

Secondary research endpoints: effectiveness endpoints: including complete response rate (CRR), objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

The study adopts the "3+3" design, that is, 3-6 subjects in each group complete the administration, and the dose group determined as the maximum tolerated dose (MTD) is included in the group of 6 subjects, totaling 9-18 example. The dose planned to be explored is the daily oral dose of the BTK inhibitor abutinib, which is 100 mg, 150 mg and 200 mg, respectively. The doses of other drugs in the plan will not be escalated.

After the last subject in each dose group completes the 28-day restricted toxicity (DLT) assessment window after the administration, the investigator can start the entry into the next dose group after evaluating and agreeing to enter the next dose group based on clinical safety data.DLT was defined as any grade 3 or higher nonhematologic toxicity, any grade 4 hematologic toxicity, grade 3 febrile neutropenia, and grade 3 thrombocytopenia with significant bleeding.

When 1 case of DLT occurs among 3 subjects in a certain dose group, 3 subjects need to be added to the same dose group (6 subjects in this dose group complete the DLT assessment): If the additional 3 subjects are tested If there is no DLT, continue the dose escalation; if 1 of the 3 increased subjects has DLT, stop the dose escalation; if the increased 3 subjects have \>1 of the subjects DLT, the dose escalation is stopped, and the dose needs to be lowered to continue to enroll 3 subjects for DLT evaluation. If DLT occurs in 2 of the 3 or 6 subjects in the dose group, then the previous low dose is defined as the maximum tolerated dose (MTD).

The extended treatment phase :

Primary study endpoints: objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) .

Secondary endpoints: time to disease progression (TTP), median survival (MST), adverse reactions (ADR), quality of life (QOL) .

The study adopts an open, one-arm, prospective clinical collaborative study . The initial treatment is BTK inhibitor (Obutinib), PD-1 monoclonal antibody combined with formustine ：Orelabrutinib continues to be taken orally until the tumor is relieved for 3 months; PD-1 monoclonal antibody is used by intravenous drip, 21 days as a treatment cycle, and a total of 1 year of observation; formustine is used by intravenous drip for 21 days It is a treatment cycle, a total of 6 cycles of observation; after 2 cycles, the efficacy is evaluated, and adverse reactions are recorded. At the same time, MTX 12mg+Ara-C 50mg+Dex 5mg was injected into the CSF cytology-positive sheath, and intrathecal injection once per treatment cycle, a total of 6 times.

Second stage treatment ：The efficacy was evaluated after 6 cycles of treatment in the initial stage. The CR patients continued to take orally abutinib (150mg, qd) for three months, and the PD-1 monoclonal antibody was used for maintenance treatment for up to 1 year; the PR patients received whole brain radiotherapy (WBRT), and at the same time Continue oral obritinib (150mg, qd) for three months and PD-1 monoclonal antibody maintenance treatment for up to one year; SD and PD patients choose methotrexate + pemetrexed combined chemotherapy for 4 cycles followed by whole brain radiotherapy (WBRT). WBRT: Regardless of age, supplementary WBRT 30-36Gy + partial reduction field irradiation up to 45Gy.

A Prospective Clinical Study of BTK Inhibitor, PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma

A Prospective Clinical Study of a New Generation of BTK Inhibitors Combined With PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma

Mingzhi Zhang

the director of oncology department of the first affiliated hospital

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pancreatic Cancer Screening in a Population at High Risk	NCT06330441	Pancreatic Duct... Hereditary Dise... Pancreatitis, C...	endoscopic ultr... magnetic resona... laboratory exam...	18 Years -	Masaryk Memorial Cancer Institute
A Prospective Clinical Study of BTK Inhibitor, PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma	NCT04831658	Primary Central...	the dose-escala...	18 Years - 69 Years	Zhengzhou University
A Prospective Clinical Study of BTK Inhibitor, PD-1 and Formustine in the First-line Treatment of Primary Central Nervous System Lymphoma	NCT04831658	Primary Central...	the dose-escala...	18 Years - 69 Years	Zhengzhou University

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