Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Fibrolamellar Carcinoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Inflammatory Agents

Anti-Infective Agents

Hematinics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Prednisone

Lenograstim

Mycophenolic Acid

Tacrolimus

Liver Extracts

Antilymphocyte Serum

Mesna

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Calcineurin Inhibitors

Enzyme Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Antitubercular Agents

Protective Agents

Patients receive living related donor partial liver transplantation performed according to standard practices. Patients will be maintained on tacrolimus, MMF, and prednisone after liver transplantation.

Upon recovery, patient must undergo eligibility screening for bone marrow transplantation (BMT).

If eligible, patients will begin:

Antithymocyte globulin (ATG): Day -16 to Day -14; fludarabine: Days -6 to Day -2 low-dose cyclophosphamide: Day -6 and -5. Tacrolimus, mycophenolate mofetil (MMF), and prednisone: day -7 and day -6. Total body irradiation on Day -1 Bone marrow infusion on Day 0. High dose cyclophosphamide plus MESNA: Day 3 and 4th Filgrastim, tacrolimus,MMF, and prednisone: Day 5 until neutrophil counts recover.

Patients followed up through post transplant day 60, then weekly following discharge.

HLA matched or haploidentical related living donor partial liver transplant followed by tacrolimus, prednisone, and MMF immunosuppression for \>3 wks

living related donor partial liver transplantation

200 cGy total body irradiation (TBI) on Day -1.

Total body irradiation

BMT using cells from the same Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor will be performed on Day 0

Bone marrow transplant from same donor

Pre-transplantation low dose cyclophosphamide given day -6 and -5 Post-transplantation high dose cyclophosphamide (PTCy; 50 mg/kg/day) will be administered on Days 3 and 4 with hydration

administered daily starting on Day 5 until absolute neutrophil count (ANC) recovery

Filgrastim

Given after liver transplant for through day -7, stopped on day -6 and restarted on day 5 post BMT

mycophenolate mofetil

Given from Day -16 to Day -14 prior to bone marrow transplantation on day 0

Antithymocyte globulin

fludarabine given from Days -6 to Day -2 before BMT

fludarabine

This trial is a phase II, single arm, open-label, single center study to assess a reduced-intensity conditioning regimen, bone marrow transplantation and high dose PTCy in recipients of a partial liver allograft from a Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor in patients with HCC.

The primary objective of this trial is to characterize recurrence-free survival at 1 year following bone marrow transplantation among recipients of prior partial liver transplantation from the same donor.

The purpose of this study is to characterize the safety and anti-tumor efficacy of sequential partial liver transplantation followed by bone marrow transplantation from the same living related donor. This treatment applies to patients whose cancer remains confined to the liver but is too widespread to be removed by surgery or treated by a liver transplant from a deceased donor. The purpose of this combined treatment is to reduce the risk of the cancer coming back after the liver transplant The bone marrow transplant may reduce the risk of cancer relapse in two ways. First, patients who have combined bone marrow and solid organ transplants may be able to get off all anti-rejection drugs, which inhibit the immune system from destroying cancer cells. Second, the donor's bone marrow contains cells of the immune system, which can attack any cancer cells that remain after the liver transplant.

This trial is a phase II, single arm, open-label, single center pilot study to assess a reduced-intensity conditioning regimen, bone marrow transplantation and high dose post-transplantation cyclophosphamide (PTCy) in recipients of a partial liver allograft from a Human Leukocyte Antigen (HLA)-matched or -haploidentical living related donor in patients with HCC. The trial includes analyses of tumor characteristics and the number and phenotype of tumor infiltrating lymphocytes in the explanted tumor. The trial also includes periodic monitoring of circulating hepatocytes to correlate with tumor response.

The study is expected to take two years to complete accrual of six patients, and the primary objective of this trial is to characterize recurrence-free survival at 1 year following bone marrow transplantation among recipients of prior partial liver transplantation from the same donor. Secondary objectives include documenting percentage of patients who become tolerant of the transplanted liver, i.e. off immunosuppression for \>6 months without biochemical evidence of liver rejection, and characterizing the relationship between donor chimerism and transplantation tolerance.

Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Hepatocellular Carcinoma (HCC)

Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Fibrolamellar or Non-fibrolamellar Hepatocellular Carcinoma (HCC) Including Fibrolamellar HCC

The proportion of transplanted participants who remain free of disease recurrence for 1 year post bone marrow transplantation

The proportion of participants who are off immunosuppression without GVHD or liver rejection at 1 year after bone marrow transplantation.

Disease-free is defined as the lack of radiographic evidence of recurrence by computed tomography or MRI.

Determine the cumulative incidences of acute grades II-IV, III-IV and chronic graft-versus-host disease

Proportion of transplanted participants who die

Determine the proportion of transplanted participants with liver allograft rejection demonstrated by a biopsy or clinically if a biopsy cannot be performed.

Fibrolamellar Cancer Foundation

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Amino Acids

Immunomodulating Agents

Durvalumab

Antineoplastic Agents, Immunological

Glutamine

Patients will receive treatment on Day 1 of each cycle. Durvalumab (1500 mg) will be administered IV on Day 1 of each cycle every 28 days.

Patients will receive treatment twice a week of each cycle. DRP-104 (145 mg,125mg, 105mg, 85mg or 65mg) will be administered subcutaneous injection twice a week of each 28 day cycle.

DRP-104

Colleen Apostal, RN

Joann Santmyer, RN

Marina Baretti, MD

The purpose of this study is to determine whether the combination of subcutaneous DRP-104 in combination with intravenous Durvalumab is safe and yields a clinically compelling antitumor activity measured as based on objective response rate (ORR, assessed by RECIST 1.1). Secondary objectives include progression-free survival (PFS) and overall survival (OS).

DRP-104 (Glutamine Antagonist) in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)

A Phase 1b/2 Study of Glutamine Antagonist DRP-104 in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Hepatocellular Carcinoma (FLC)

When calculating the incidence of AEs, each AE (as defined by NCI Common Terminology Criteria for Adverse Events \[CTCAE\] v5.0) will be counted only once for a given subject.

ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) to DRP-104 (glutamine antagonist) in combination with duvalumab, based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.

PFS is defined as the number of months from the date of first treatment to disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Progression will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.

OS is defined as the number of months from the first dose of study treatment to death from any cause or end of follow-up. OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis. Estimation based on the Kaplan-Meier curve.

Dracen Pharmaceuticals, Inc.

Symptoms and General Pathology

Neoplasm Metastasis

Cholangiocarcinoma

Klatskin Tumor

Bile Duct Cancer

Gallbladder Cancer

Intrahepatic Cholangiocarcinoma

Participants' cases are discussed in tumor conference without the use of ADBoard, according to conventional practice.

Participants' cases will be evaluated by ADBoard directly before they are discussed in the tumor conference.

Utilizing the clinical decision support system 'ADBoard' for therapy selection in participants with hepatobiliary tumors

ADBoard

Felix Krenzien

Christian Benzing

The goal of this observational study is to compare the recommendations of the artificial intelligence clinical decision support system 'ADBoard', with the recommendations of physicians by tumor conferences in patients with hepatobiliary tumors. The main questions it aims to answer are:

Can ADBoard achieve a high level of similar recommendations as physicians' tumor conferences? Can ADBoard consider a more complete set of patient-related data than in physicians' tumor conferences? Can ADBoard reduce the time between the first time the patient is discussed at the tumor conference and the start of the recommended treatment plan? Participants will have their hepatobiliary tumor treatments determined by either tumor conference with ADBoard, or tumor conference without ADBoard.

The ADBoard study is a monocentric, prospective, parallel randomized controlled trial with a non-inferiority framework. Participants will be randomized 1:1 into one of two groups: either a) tumor conference with ADBoard, or b) tumor conference without ADBoard.

Therapeutic Assistance and Decision-making Algorithms in Hepatobiliary Tumor Boards

Evaluation of the Trustworthiness of the Application of Artificial Intelligence and Decision Support Systems for the Creation of Tumor Conference Protocols

Examples of possible treatment recommendations are liver resection (curative), regimen of chemotherapy, immunotherapy, radiotherapy, transarterial chemoembolisation, diagnostics, best-supportive care, follow-up by re-presentation.

The interrater reliability of the recommendations of ADBoard and the tumor conferences with regard to their agreement will be measured.

The intrarater reliability will be measured by testing all participant cases several times by the ADBoard according to the required sample size with sufficient statistical power (test-retest). Interrater and intrarater reliability will be evaluated descriptively (percentage of agreement, contingency tables), and finally the Cohen-Kappa value will be assessed.

For each type of tumor examined, a series of relevant parameters is defined by the medical staff. The objective is achieved if complete documentation, defined as documentation status 'present' or 'detected as missing', is present in more than or equal to 75% of all ADBoard-assisted decisions.

The System Causability Scale will be reviewed by 3 specialist physicians. The score ranges from 0 to 1. A higher score means greater suitability of the user interface, explanation, or explanation process itself for the intended purpose of tumor conference treatment recommendations.

The time between the initial presentation of the case to the tumor conference and the time of recommendation implementation will be recorded.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sequential, Related Donor Partial Liver Transplantation Followed by Bone Marrow Transplantation for Hepatocellular Carcinoma (HCC)	NCT02702960	Fibrolamellar H... Hepatocellular ... Hepatocellular ...	living related ... Total body irra... Bone marrow tra... Cyclophosphamid... Mesna Filgrastim Tacrolimus mycophenolate m... Prednisone Antithymocyte g... fludarabine	16 Years - 65 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
DRP-104 (Glutamine Antagonist) in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)	NCT06027086	Fibrolamellar H...	Durvalumab DRP-104	12 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
DRP-104 (Glutamine Antagonist) in Combination With Durvalumab in Patients With Advanced Stage Fibrolamellar Carcinoma (FLC)	NCT06027086	Fibrolamellar H...	Durvalumab DRP-104	12 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Therapeutic Assistance and Decision-making Algorithms in Hepatobiliary Tumor Boards	NCT05681949	Hepatocellular ... Fibrolamellar H... Cholangiocarcin... Intrahepatic Ch... Metastasis to L... Gallbladder Car...	ADBoard	18 Years -	Charite University, Berlin, Germany
Therapeutic Assistance and Decision-making Algorithms in Hepatobiliary Tumor Boards	NCT05681949	Hepatocellular ... Fibrolamellar H... Cholangiocarcin... Intrahepatic Ch... Metastasis to L... Gallbladder Car...	ADBoard	18 Years -	Charite University, Berlin, Germany

Spots Global Cancer Trial Database for fibrolamellar hepatocellular carcinoma