Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Jaundice

Bile Duct Neoplasms

Jaundice, Obstructive

Hyperbilirubinemia

Skin Manifestations

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Gastrointestinal Diseases

bilateral parallel stent insertion (right and left side)

parallel stent

Bilateral Y-stent insertion (stent in stent type)

Y-stent (BONASTENT M-Hilar)

Kwang hyuck Lee, MD, phD

Internal biliary drainage using stent is used for malignant hilar obstruction such as cholangiocarcinoma, hepatocellular carcinoma and other malignancy including metastasis.

Bilateral drainage is more physiologic and have more long patency than unilateral drainage.

There are two methods of bilateral drainage: Y-stent and side by side.

However there are no clinical data about comparing the effectiveness of these two methods.

Therefore the investigators want to compare the clinical outcomes of two methods:

Y-stent and side by side.

Comparison Between Two Methods of Bilateral Stenting for Malignant Hilar Obstruction

Samsung Medical Center

Assistant Professor of Medicine

Gland and Hormone Related Diseases

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Pancreatic Neoplasms

Adenoma

Cholangitis

Constriction, Pathologic

Cholestasis

Cholangitis, Sclerosing

Adenoma, Bile Duct

Papilloma, Intraductal

Cholestasis, Extrahepatic

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pathological Conditions, Anatomical

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Bile Duct Cancer

Primary Sclerosing Cholangitis

Experienced Endoscopists with significant user experience with Volumetric Laser Endomicroscopy for bile duct/pancreatic duct strictures

Experienced Endoscopists with non-significant or beignner user experience with Volumetric Laser Endomicroscopy for bile duct/pancreatic duct strictures

Interobserver agreement or Interrater agreement using 9 visual criteria for diagnosing VLE clips that feature indeterminate biliary or pancreatic duct strictures

Interobserver agreement or Interrater agreement

Michel Kahaleh, MD

The purpose of this study is to assess the interobserver agreement (IOV) for pancreatico-biliary Volumetric Laser Endomicroscopy (VLE) de-identified clips using the new VLE criteria.

This is an Interobserver study to validate VLE criteria for indeterminate biliary and pancreatic duct strictures and evaluate impact on clinical management.

Objective: Validate diagnostic impact of VLE diagnostic accuracy on clinical management

Primary Objectives:

1. Interobserver study for criteria validation and accuracy, Positive predictive value (PPV) and Negative predictive value (NPV), sensitivity and specificity.
2. Evaluation of VLE diagnostics on clinical management (increased accuracy/faster detection)
3. Determination of learning curve to standardize credentialing for endoscopists to use and interpret VLE imaging for biliary/pancreatic treatment management.

B. Hypotheses / Research Question(s) The new VLE criteria for biliary and pancreatic duct strictures increase accuracy, thus leading to substantial impact on clinical management (Screening and Treatment)

Study Design (2 phase):

* Phase 1: Primary Objective 1 and 2 part of the study will be completed.
* Phase 2: Primary Objective 3 of the study will be conducted within 1 month.

Study Timeline: 3 months post WIRB approval. Sample size: 40 VLE Clips of at least 20 seconds featuring one or more the VLE criteria. All clips will have confirmed diagnosis for accuracy analysis. All clips will be de-identified. All clips will be removed from RedCAP and other secure cloud storage upon completion of study.

Clips will be supplied by NinePoint Medical, the company behind VLE OCT. All VLE clips will be from a dataset of clips collected from adults \> 18 and who underwent Endoscopic retrograde cholangiopancreatography (ERCP) with indeterminate biliary stricture indications. The clips are chosen based on the quality of the clips, duration, final diagnosis and presence of either benign or malignant criteria.

Investigators: Up to 30 Expert and non-expert endoscopists currently using VLE

Volumetric Laser Endomicroscopy's (VLE) Diagnostic Accuracy Validation Study: Impact on Clinical Management Study

Interobserver study for criteria validation and accuracy, PPV and NPV, sensitivity and specificity

Correlation analysis of any of the 9 visual criteria with malignancy diagnosis as determined by endoscopist

Learning curve using CUSUM analysis to standardize credentialing for endoscopists to use and interpret VLE imaging for biliary/pancreatic treatment management proficiently.

NinePoint Medical

Innovative Digestive Health Education and Research Inc

Biliary Tract Cancer

All Drugs and Chemicals

Endothelial Growth Factors

Mitogens

Tivozanib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tivozanib, P.O. daily at 0.89 mg (given on Days 1-21 of every 28-day cycle) with intra-patient escalation to 1.34 mg daily (given on Days 1-21 of every 28-day cycle) and possible dose de-escalation to 0.89 mg every other day (without interruption for a 28-day cycle) if needed to determine RP2D

Tivozanib at the RP2D established in Phase I

Oral tivozanib taken daily for Days 1-21 continuously (of each 28-day cycle) followed with 7 days off medication (except for patients in DL-1, with dosing every other day of the 28-day cycle). Phase I: The starting dose (DL1) is 0.89 mg taken once a day continuously for Days 1-21 with 1 week off medication (except for those patients assigned to DL-1, where tivozanib should be taken every other day, around 48 hours apart in 28-day cycle). Patients may escalate to 1.34 mg taken once a day (DL2) continuously for Days 1-21 with 1 week off medication for their second cycle if there are no dose-limiting toxicities. Phase II: Tivozanib dose level will be at the recommended Phase II dose (RP2D) established in Phase I.

Kathleen M Smith, R.N.

Jonathan M Hernandez, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

Cholangiocarcinoma (CCA) is an aggressive cancer of the bile ducts. People with CCA have few treatment options and poor survival. Researchers want to see if a new drug can stop or slow CCA growth.

Objective:

To find the safest and most effective dose of tivozanib to treat CCA and learn its overall response rate.

Eligibility:

Adults ages 18 and older with CCA not removable with surgery and have been treated with at least one type of chemotherapy.

Design:

Participants will be screened with the following:

* Medical history
* Physical exam
* Assessment of their ability to do daily activities
* Medicine review
* Blood tests, including thyroid function tests
* Urine tests
* Electrocardiogram, to check heart function
* Pregnancy test, if needed
* Tumor biopsy, if needed
* Computed tomography scans
* Magnetic resonance imaging, if needed

Some screening tests may be repeated during the study.

Participants will be asked to enroll in protocol #13C0176. This will allow any remaining tumor or blood samples to be used in future research.

Participants will take tivozanib by mouth, once a day for 21 days per cycle or every other day per cycle. Each cycle is 28 days. They can take the drug until they have bad side effects, their CCA gets worse, or if they become pregnant. They will record their blood pressure twice daily at home. They will also keep a medication diary of each dose of tivozanib they take and any side effects.

Participants will have study visits before starting each new cycle and every 8 weeks. They will also have a follow-up visit 30 days after treatment ends at NIH, or if they are unable to come to NIH by phone, videocall, or other NIH-approved platform. Then they will be contacted 6 and 12 months later, and then once a year.

Background:

Biliary Tract Cancers (BTC) (cholangiocarcinoma (CCA) and gallbladder cancer (GBC)) are aggressive malignancies that remain a clinical challenge with limited treatment options and poor survival. Combination chemotherapy with gemcitabine and cisplatin is the most validated first-line treatment, but the response rate approaches only 22% and median progression free survival is 8 months.

Cytoplasmic accumulation of the nuclear export protein exportin 7, XPO7, portends poor outcomes for patients with biliary tract cancer. Using pre-clinical models, we established XPO7 as an oncogenic driver in CCA cells and determined that this biology is driven by the interaction between XPO7 and a hitherto incompletely studied kinase, Ste-20 like kinase (SLK).

XPO7 binds to and promotes cytoplasmic localization and stabilization of SLK, which in turn activates oncogenic signaling. Targeting SLK expression via short hairpin RNA abrogates tumor formation in 3D culture and mice models, establishing SLK as a novel

target in biliary tract cancer.

The pan-vascular endothelial growth factor receptor (VEGFR) inhibitor tivozanib demonstrated activity against SLK in our in vitro screen, which we later confirmed with x-ray crystallography. Tivozanib abrogated growth of CCA tumorspheres, resulting in substantial tumor regression using murine xenograft models and patient-derived xenografts. Additionally, we evaluated tivozanib in our ex vivo tumor platform using a liver metastasis from a patient with XPO7-expressing biliary tract cancer and documented tumor cell apoptosis.

As reliable, molecular-targeted regimens either for first- or second-line therapy for the majority of patients with biliary tract cancer have remained elusive, these results support evaluation of tivozanib as a treatment option for patients with biliary tract cancer.

Objectives:

Determine the overall response rate (RECIST) of tivozanib in patients with biliary tract cancer (BTC) who were previously treated with first-line therapy.

Eligibility:

Patients with histologically or cytologically confirmed biliary tract cancer (BTC) not amenable to resection

Previous treatment with 1st line chemotherapy

Age \>= 18 years of age

ECOG performance status of \<=2

Preserved hepatic function

Adequate organ and marrow function

Design:

Open-label, single-center, non-randomized Phase II study

Trial is a Simon minimax two-stage Phase II trial design to determine efficacy.

Treatment is in cycles of 28 days, 3 weeks on, 1 week off (with possible dose de-escalation if needed). Treatment evaluations for efficacy will be every 2 months (8 weeks).

Accrual ceiling will be set at 24 patients

Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers

Phase II Study Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.

Patients will be re-evaluated for response every 8 weeks after start of treatment. The Phase II clinical response rate (CR+PR) will be determined and reported along with a 95% confidence interval.

List of adverse event frequency and grade. Patient DLTs will be counted and reported to determine the safety and tolerability of tivozanib and to establish the recommended Phase II dose (RP2D) using a standard 3+3 design.

CT or MRI will be used for response criteria. PFS and OS will be determined using Kaplan-Meier estimates.

CT or MRI will be used for response criteria. DCR (CR plus PR plus SD) will be determined and reported along with 95% confidence intervals. Wherever possible, duration of DCR will be reported.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Comparison Between Two Methods of Bilateral Stenting for Malignant Hilar Obstruction	NCT01622803	Bile Duct Neopl... Obstructive Jau...	parallel stent Y-stent (BONAST...	18 Years -	Samsung Medical Center
Volumetric Laser Endomicroscopy's (VLE) Diagnostic Accuracy Validation Study: Impact on Clinical Management Study	NCT03951324	Biliary Strictu... Pancreas Cancer Cholangiocarcin... Bile Duct Cance... Bile Duct Neopl... Bile Duct Neopl... Bile Duct Lesio... Bile Duct Obstr... Bile Duct Disea... Bile Duct Obstr... Bile Duct Steno... Bile Duct Adeno... Pancreatic Duct... Pancreatic Duct... Pancreatic Duct... Pancreatic Duct... Primary Scleros...	Interobserver a...	18 Years -	Innovative Digestive Health Education and Research Inc
Evaluating Efficacy of Tivozanib (AV-951) in Biliary Tract Cancers	NCT04645160	Cholangiocarcin... Bile Duct Neopl... Biliary Tract M...	Tivozanib	18 Years -	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for bile duct neoplasm