Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Pancreatic Neoplasms

Constriction, Pathologic

Cholestasis

Bile Duct Neoplasms

Cholestasis, Extrahepatic

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Bile Duct Diseases

Biliary Tract Diseases

Biliary Tract Neoplasms

Pancreatic Cancer

Bile Duct Cancer

Patients will receive two 8.5Fr Platic biliary stents placed side by side across the biliary stricture.

Patients will receive a fully covered Self-expandable Metal Stents (10mm) across the biliary stricture

Palliation of malignant biliary obstruction

Biliary stent

Marc M Bernon, MBBCh

A randomised clinical trial to compare the clinical efficacy of multiple plastic stents to fully covered self expanding metal stents in the palliation of distal malignant biliary obstruction in patients with irresectable tumours.

Self-expandable Metal Stents Versus Multiple Plastic Stents for Palliation of Biliary Obstruction

Treatment of Malignant Distal Biliary Obstruction - a Randomized Study

Number of patients without Stent failure (jaundice) or death with a patent stent

Number of patietns alive in each group at 12 months

Number of patients in whom there was failure to deploy the assigned stent(s) after randomisation

The differance in treatment costs between the two groups, measured in USD

University of Cape Town

Senior consultant

Carcinoma

Neoplasm Metastasis

Gallbladder Diseases

Biliary Tract Cancer

Gallbladder Cancer

Hematinics

All Drugs and Chemicals

Liver Extracts

Regorafenib is administered as monotherapy during the study. 160 mg once daily (QD) will be administered for 3 weeks on /1 week off. One cycle is 28 days.

Four 40 mg regorafenib tables should be taken in the morning with approximately 8 fluid ounces (240 mL) of water after a low-fat (\<30% fat) breakfast.

Regorafenib

Richard Kim, M.D.

The main purpose of this study is to see if regorafenib can help control or decrease cancer size in patients with cancer of the bile duct. Researchers also want to find out if regorafenib is safe and tolerable.

Single Agent Regorafenib in Refractory Advanced Biliary Cancers

Multi Institutional Phase II Trial of Single Agent Regorafenib in Refractory Advanced Biliary Cancers

OS will be defined as the time from starting on trial to date of death due to any cause. The final analysis will be conducted after the follow-time of the last patient exceeds 6 months.

DCR defined as Complete Response (CR) + Partial Response (PR)+ Stable Disease (SD). CR: Complete disappearance of all target and non-target lesions (with the exception of lymph nodes mentioned below); No new lesions. PR: Applies only to patients with at least one measurable lesion; Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions; No unequivocal progression of nonmeasurable disease; No new lesions. SD: Does not qualify for CR, PR, Progression or Symptomatic Deterioration.

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.

Progression - One or more of the following must occur: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site.

Bayer

H. Lee Moffitt Cancer Center and Research Institute

Regorafenib is administered as monotherapy during the study. 160 mg once daily (QD) will be administered for 3 weeks on /1 week off. One cycle is 28 days.

Regorafenib: Four 40 mg regorafenib tables should be taken in the morning with approximately 8 fluid ounces (240 mL) of water after a low-fat (\<30% fat) breakfast.

Regorafenib Monotherapy

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Richard Kim, MD

Patients that were evaluable for efficacy

Overall Survival (OS) at 6 Months

Disease Control Response (DCR)

Progression Free Survival (PFS)

Overall Study

Cholangiocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Antineoplastic Agents

Capecitabine

Pembrolizumab

Immunomodulating Agents

Oxaliplatin

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Keytruda, oxaliplatin, capecitabine and escalating doses of CDX-1140

Keytruda, oxaliplatin, capecitabine and estimated safe dose of CDX-1140

Oxaliplatin (130 mg/m2) will be administered IV on Day 1 of each cycle, every 21 days (up to 6 cycles).

oxaliplatin

Capecitabine (750 mg/m2 every 12 hours) will be administered orally with an intermittent schedule: 2 weeks on, 1 week off, of each cycle, every 21 days (up to 6 cycles).

capecitabine

Pembrolizumab (200 mg) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).

Keytruda

CDX-1140 (0.36-1.5 mg/kg; per assigned dose level) will be given IV on Day 8 of each cycle every 21 days (up to 6 cycles).

CDX-1140

Donna M Hrones, C.R.N.P.

Maria C Monge Bonilla, M.D.

National Cancer Institute Referral Office

Background:

Biliary tract carcinoma (BTC) is cancer of the slender tubes that carry fluids in the liver. People with advanced BTC have few treatment options, and their survival rates are very low.

Objective:

To test a study drug (CDX-1140) combined 3 other drugs (capecitabine, oxaliplatin, Keytruda) in people with BTC.

Eligibility:

Adults aged 18 years or older with BTC that progressed after treatment and is not eligible for surgery or liver transplant.

Design:

Participants will be screened. They will have a physical exam. They will have blood tests and tests of their heart function. They will have imaging scans. They may need to have a biopsy: A small sample of tissue will be taken from their tumor using a small needle.

Three of the drugs are given through a tube attached to a needle inserted into a vein in the arm (intravenous). The fourth drug is a pill taken by mouth with water.

Participants will be treated in 21-day cycles. They will receive intravenous treatments on day 1 and day 8 of the first 6 cycles. After that, they will receive intravenous treatments only on day 1 of each cycle.

Participants will take the pill twice a day only for the first 2 weeks of each cycle. They will stop taking this drug after 6 cycles.

Imaging scans will be repeated every 9 weeks.

Participants may continue receiving the study treatment for up to 2 years. Follow-up visits, including imaging scans, will continue for 3 more years. These images may be taken at other locations and sent to the researchers.

...

Background:

Advanced biliary tract carcinoma (BTC) has limited treatment options in the second line setting and a dismal prognosis.

Capecitabine and oxaliplatin (CAPOX) in combination with Keytruda is a tolerable and potentially effective treatment for patients with refractory advanced BTC.

Programmed cell death protein 1 (PD-1) is an inhibitory receptor that is expressed by all Tcells during activation. It regulates T-cell effector functions during various physiological responses, including acute and chronic infection, cancer and autoimmunity, and immune

homeostasis. Keytruda is a programmed death receptor-1 (PD-1)-blocking antibody indicated for the treatment of different cancers including patients with hepatocellular carcinoma.

CD40-mediated activation of macrophages and dendritic cells (DC)s in intrahepatic cholangiocarcinoma (iCCA) significantly improves response to anti-PD-1 therapy in preclinical studies. The efficacy of this regimen is enhanced by first-line chemotherapy,

supporting the potential antitumor efficacy of the combination of CD40 agonist antibody (anti-CD40) with anti-PD-1 and chemotherapy.

Objectives:

Phase I: To estimate safe dose of CDX-1140 used in combination with CAPOX, and Keytruda (R)

Phase II:

To evaluate the 6-month progression free survival (PFS) in participants with advanced BTC treated with CDX-1140, CAPOX, and Keytruda (R).

To determine the overall response rate (ORR) defined as complete response (CR) + partial response (PR) according to RECIST 1.1 in participants with advanced BTC.

Eligibility:

Histopathological confirmation of BTC or histopathological confirmation of carcinoma in the setting of clinical and radiological characteristics which, together with the pathology,are highly suggestive of a diagnosis of BTC

Age \>=18 years

Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Design:

Phase I/II, single-arm, non-randomized trial of Keytruda(R) and CDX-1140 in combination with CAPOX in participants with BTC in the second-line setting.

Initially, 9-12 participants will be enrolled into a Phase I portion of the trial. If safe, we will continue enrollment as planned into Phase II, if not, we will close the protocol.

After estimation of CDX-1140 recommended phase II dose, the first 13 participants enrolled at this dose level of CDX-1140 in Phase I and Phase II will be evaluated forprogression. If among these 13 participants, no more than 2 can be progression-free at the 6-months evaluation, then no further participants will be enrolled as soon as this can be determined.

A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)

A Phase I/II Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)

.All IPD recorded in the medical record will be shared with intramural investigators upon request. 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. All collected IPD will be shared with collaborators under the terms of collaborative agreements.

Estimation of safe dose will be determined based on number of dose limiting toxicities (DLTs) experienced.

6-month PFS probability will be calculated using the Kaplan-Meier method.

The fraction of participants who experience a response (PR + CR) evaluated every 9 (+/- 4) weeks. Results will be reported along with 80% and 95% two-sided confidence intervals.

Any adverse events/toxicities identified will be reported by type and grade.

Participants will be assessed for survival at study visits while on study therapy and annually thereafter.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Self-expandable Metal Stents Versus Multiple Plastic Stents for Palliation of Biliary Obstruction	NCT03821025	Bile Duct Obstr... Cancer of the P... Cancer of the B... Biliary Strictu...	Biliary stent	18 Years -	University of Cape Town
Single Agent Regorafenib in Refractory Advanced Biliary Cancers	NCT02115542	Cancer of the B...	Regorafenib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)	NCT05849480	Biliary Cancer Bile Duct Cance... Cancer of the B...	oxaliplatin capecitabine Keytruda CDX-1140	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
A Study of CDX-1140, a CD40 Agonist, in Combination With Capecitabine and Oxaliplatin (CAPOX) and Keytruda in Subjects With Biliary Tract Carcinoma (BTC)	NCT05849480	Biliary Cancer Bile Duct Cance... Cancer of the B...	oxaliplatin capecitabine Keytruda CDX-1140	18 Years - 120 Years	National Institutes of Health Clinical Center (CC)
Self-expandable Metal Stents Versus Multiple Plastic Stents for Palliation of Biliary Obstruction	NCT03821025	Bile Duct Obstr... Cancer of the P... Cancer of the B... Biliary Strictu...	Biliary stent	18 Years -	University of Cape Town

Spots Global Cancer Trial Database for cancer of the bile duct