Chronic Pancreatitis

Evaluate the safety of the novel FAP targeted molecular probe 18F-FAPI-YQ104 labeled with radioactive isotopes in clinical applications and verify its effectiveness in tumor diagnosis.

Part 1 will determine the biodistribution, dosimetry, optimal dose (radioactivity) and imaging time window of 64Cu-LNTH-1363S in 6 evaluable patients with supposed FAP-expressing solid tumors (metastatic sarcomas). All six patients will receive 8 ± 1 mCi (\~90 μg mass dose) in this study. All images will undergo analysis by blinded central readers. Optimal radioactivity and timing window will be determined based on image quality scores and measured tumor-to-background ratio. Part 1 of the study will last approximately 3 weeks for each patient and includes a Screening Period (up to 14 days), a 1-day Intervention Period and a Safety Follow-up Period (7 days post dose). Part 2 will evaluate 64Cu-LNTH-1363S correlation with FAP expression measured by IHC (SUVmax and SUVmean vs IHC score) in 20 evaluable patients with non-metastatic, operable, supposed FAP-expressing solid tumors (sarcomas, esophageal, gastric, pancreatic, colorectal) planned for surgery within 60 days (from study imaging). If the optimal radioactivity determined from Part 1 is less than 8 ± 1 mCi, the first 6 patients in Part 2 will be used to validate this optimal radioactivity. Part 2 of the study will last approximately 10 to 11 weeks and includes: a Screening Period (up to 14 days), a 1-day Intervention Period, a 1 day Safety Followup Period (Day 2) and a Scheduled Surgery IHC Sample Collection Period (from Day 2 to Day 60). Both Part 1 and Part 2 of the study will also monitor cardiac safety by detecting changes in HR, T wave, ST segment and other ECG parameters and characterizing the concentration-response relationship of 64Cu-LNTH-1363S for QT and corrected QT interval (QTc) prolongation.

At present, radiopharmaceuticals targeting FAP have been developed for the diagnosis and treatment of various tumors. Considering the problems of fast tumor tissue clearance and short retention time in small molecule FAP inhibitors based on quinoline rings, this project optimized their ligands and developed a new FAP targeted technetium labeled molecular imaging probe for SPECT/CT imaging research to evaluate its safety in clinical application and its effectiveness in tumor diagnosis.

Pancreaticobiliary cancer patients have a dismal prognosis. Therefore, patient stratification for the proper primary treatment is crucial to prevent unnecessary surgery and opens up the opportunity for novel (multimodal) treatment. Unfortunately, conventional imaging modalities are not sensitive enough to detect small tumor lesions or differentiate between benign and malignant tissue after neoadjuvant therapy. Tumor-specific imaging, using PET/CT imaging, can identify tumor tissue more accurately and therefore can improve lesion detection and patient stratification. Fibroblast activation protein (FAP) shows promise as a target to identify pancreaticobiliary cancers, lymph node metastases, and residual disease after neoadjuvant therapy. The FAP targeted inhibitor (FAPI) is developed to target FAP and has been labelled to the Gallium-68 (68Ga) radioisotope, resulting in the \[68Ga\]Ga-FAPI-46 tracer. This study will be a three part monocenter study focusing on the clinical evaluation of \[68Ga\]Ga-FAPI-46. * In part A, the pharmacokinetics of this tracer will be studied and the simplified method(s) to quantify tracer uptake will be validated. * In part B, a test-retest study will be performed to assess the repeatability of these simplified quantitative methods. * In part C, the sensitivity and feasibility of therapy response monitoring will be investigated.

Project Summary/Abstract Short bowel syndrome (SBS) is often due to the loss of large amounts of small intestine that compromises digestive absorption. The treatments include (1) a high-calorie diet that includes vitamins, minerals, carbohydrates, proteins and fats; (2) injections of vitamins and minerals; (3) administration of drugs to slow the normal movement of the intestine or to increase the surface area of the intestinal lining; and (4) feeding through the vein (i.e., parenteral nutrition or PN). Many patients cannot wean from PN due to reduced intestinal length or function. Patients on long-term PN frequently experience serious metabolic complications, sepsis, hepatic biliary disorders including cholestasis, and fibrosis and can progress to liver failure. Full intestinal feeding (enteral nutrition) without PN is the optimal way to prevent the above complications. Enterally administered long chain triglycerides in patients with SBS, especially those with hepatic dysfunction, are not well tolerated due to bile acid malabsorption, which leads to decreased micelle formation and fat digestion. The dietary fat is unable to be emulsified by the bile acids and acted on by lipases before exiting the patient as stool. Switching to other forms of fat such as medium-chain triglycerides (MCTs) that do not require micelles for absorption may be better tolerated in patients with bile acid or pancreatic insufficiency but are not optimal as they increase the osmotic load in the intestine. This may increase the chance of stool dumping; moreover, MCTs do not contain essential fatty acids (FAs). The ability to provide the essential FAs such as those present in enteral formulas in a form that does not require the formation of micelles for absorption, would allow patients with SBS and those who are no longer PN dependent to receive adequate nutrition and continue to maintain the same growth trajectory as when they received the majority of their nutrition parenterally. RELiZORB is a digestive enzyme cartridge connected in-line with enteral feed tubing sets designed to mimic the function of pancreatic lipase. It is hypothesized that by using an external lipase device (RELiZORB) enteral nutrition will be better absorbed, and PN dependence reduced as enteral autonomy is increased. This product uniquely eliminates the need for intestinal emulsification and lipase activity and eliminates the risk of drugs, including lipases, allowing absorption at the time the diet enters the gut. The device has been shown to digest \>90% of fat in most enteral formulas. This is a phase 3, open label single center clinical trial to determine the safety, tolerability, and bioavailability of the RELiZORB enzyme cartridge with enteral nutrition when used daily for 90 days in pediatric subjects with SBS, aged 2 years - 18 years, who are PN dependent. The change in PN calories from baseline, assessed at Day 7, 14, 28, 60, and 90, will be assessed by area under the curve and presented with a 95% confidence interval. The number (percent) of treatment-emergent adverse events, grade 2 or above, will be tabulated. Changes in growth, fecal fat, plasma FAs, PN volume, and enteral/oral nutrition will be described.

This trial was a single-arm, open-label design to evaluate the efficacy and safety of "TQB2916+ gemcitabine + albumin-paclitaxel" as the first-line treatment for metastatic pancreatic cancer.

The GENESIS study is a multicenter, prospective, non-interventional, clinical study with a target of 12,000 subjects and an anticipated total duration of 36 months. The aim of study GENESIS is to provide a pilot map of HLA genetic variation in the Greek population in order to be used in medical research and for possible clinical applications (evaluation of possible correlations with selected underlying diseases). During the study, each subject will conduct one visit to the participating cite, in which they will provide: 1. Demographic information \[i.e. date of birth, gender, race, ancestry (including information about the subject's grandparents' birthplace), height, weight\], 2. Other information about smoking/vaping, alcohol consumption, arterial blood pressure, diagnosed diseases (if any), current treatments (if any), and 3. Recent (up to 12 months prior to sample collection) results if/when are available from clinical lab tests such as blood count (Hct, Hb, RBC, WBC, PLT count), including a metabolic panel, liver enzymes and biochemical parameters (Glu, HbA1c, TC, TG, LDL-C, HDL-C, ALT, AST, ALP, γGT, bilirubin, LDH, insulin, C-peptide). Upon completion of the data registry, two buccal swabs will be collected per subject and they will be stored at ALTP premises until their shipment to Galatea.Bio. All buccal swab samples will be subjected to genetic material (DNA) extraction. The DNA samples will be further proceeded for HLA genotyping analysis. A follow up analysis will be performed in selected DNA samples via full low-pass whole genome sequencing (LP-WGS), which aims to further investigate the association between the HLA region and autoimmune diseases. Upon completion of the analysis, an individualized ancestry report will be securely made available to all study subjects which they can access, as and if they elect to.

This is a Prospective, interventional, open label, single arm, multiple center study. The study is designed to evaluate the feasibility and safety of the DaRT seeds for the treatment of advanced pancreatic cancer. The study will be comprised of a screening period, DaRT insertion visit, acute follow-up phase of 4- 8 weeks and a long-term follow up phase of 3 months. The total duration of the study will be 3 months from the DaRT insertion procedure. 15 patients with advanced pancreatic cancer will be recruited by the investigational site. Eligible patients who meet inclusion/exclusion criteria (as assessed during the screening period) will be invited to the site for the procedure of DaRT seeds insertion. The patients will be monitored for a period of 3 months post insertion

This observational study aims to (1) validate a multimodal artificial intelligence (AI) model for early detection of cancer-associated cachexia in pancreatic cancer patients and (2) assess the feasibility and acceptability of diet and exercise interventions for cachexia management. The study will use retrospective data from the Florida Pancreas Collaborative and prospective data from newly diagnosed patients at Moffitt Cancer Center.

* In an effort to overcome the major challenges of the conventional cancer cell-killing therapy for high side effect, drug resistance, cancer recurrence and tumor heterogenicity, Qurgen Inc. is developing a novel transcription factor (TF) protein anticancer drug, named SON-DP, to treat the Participants with relapsed and advanced metastatic solid tumors. Proposed as an effective therapeutic drug product for a cell-converting cancer therapy, SON-DP is expected to transform cancer cells in situ into normal tissue cells via a SON-DP induced cancer cell reprogramming and re-differentiation process as an innovative rationale. * SON-DP is developed based on the rationale of cancer cell conversion into normal tissue cells as the primary mechanism of actions of a new cancer therapy, not by cancer cell-killing, the traditional goals of chemotherapy, radiation therapy, targeted therapy and immune therapy. Cancer cell conversion is achieved by the SON-DP induced pluripotent re-programming in situ inside tumor tissue into transient iPSCs (tiPSCs) that quickly re-differentiate into normal tissue cells induced by the differentiating resident tissue environment. The in situ generated tiPSCs either secrete exosomes, providing the embryonic stem cells (ESC)-like microenvironments to transform the surrounding cancer cells into normal tissue cells for an overall malignant phenotype reversion (OMPR) (an effect named as a bystander effect), or display a targeting effect that enables the in situ generated tiPSCs to track down the distant metastatic cancer cells for OMPR (an effect named as a tropism effect). The SON-DP-induced cell reprogramming also restored the mutation-caused and compromised p53 checkpoint in cancer cells to re-establish cell quality control system that ensures the downstream re-differentiation of the in situ generated tiPSCs into normal tissue cells. Overall, this SON-DP-induced re-programming and re-differentiation process is capable of transforming both primary and metastatic cancer cells into normal tissue cells. * Preclinical studies demonstrated that treatment of tumors with SON-DP resulted in eradication of late-stage cancers and long term (over 3 years) survival without teratoma formation and cancer recurrence in multiple tumor-bearing mouse/rat (syngeneic) or human xenograft rodent models, providing high treatment efficacy of this cell-converting cancer therapy. Thus, the cell-converting cancer therapy rationale represents a new cancer therapeutic strategy. SON-DP was tolerated in tumor-bearing rodents, as well as in naïve rats, dogs, and monkeys as demonstrated by GLP-enabled (rats and dogs) and non-GLP (monkey) toxicity study and after repeated IV administrations at higher doses compared with the planned clinical dose range. Therefore, the current nonclinical studies, including pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies, support the safety and efficacy of SON-DP TF protein drug product to be used in clinical studies of human participants. This first-in-human (FIH) clinical study will be conducted in selected types of relapsed/refractory advanced/metastatic solid tumors as a step in demonstrating the utility of this anticancer agent. * In this SON-DP-A001-ST clinical trial, SON-DP is given to the participants with late stage solid tumors through 90-minutes IV infusion either once a week or twice a week at first 4 dose levels during the first Phase I dose escalation stage with the purpose to identify the final schedule (either once a week or twice a week) for the last 3 higher dose levels and the recommended phase II dose (RP2D) for the second Phase Ib does expansion stage that will focus on 4 cancer types including breast cancer, pancreatic cancer, ovarian cancer and colorectal cancer. * During Phase Ia dose escalation stage, an accelerated 3+3 design will be followed. A Safety Monitoring Committee (SMC) will be formed to evaluate all the safety, efficacy, pharmacokinetic and pharmacodynamic data of each dose level cohort to decide if the SON-DP dose level should be either escalated to the next dose level or de-escalated to one level below or determination of maximum tolerated dose (MTD) or RP2D confirmation or others. Phase Ia will enroll the participants with various types of solid tumors that metastasized and not response to standard treatment. * During Phase Ib dose expansion stage, SON-DP will be used, at RP2D dose level, to treat the participants with 4 specific cancer types including breast cancer, pancreatic cancer, ovary cancer or colorectal cancer. Four groups of cancer cohorts will be opened with eligible participants who have relapsed/refractory/intolerant to standard of care therapies of these four advanced/metastatic solid tumors. Participants will be followed for safety, confirmation of the RP2D, PK, PD, and anti-tumor activity as measured by standard assessment tools.