Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Cholangiocarcinoma is a fatal malignant neoplasm originating from biliary tracts and constitutes about 5-10% of primary liver cancers, characterized by a poor prognosis. High prevalence in southeast and eastern Asia has been observed. At present, the cellular and molecular mechanisms leading to oncogenesis of cholangiocarcinoma remain unclear.

The RAS gene product has a key role in controlling cell growth and differentiation through its intrinsic GTPase activity. Point mutations that activate the RAS protein and its downstream cascade have been observed in human tumors. Both KRAS and BRAF are members of the RAS-RAF-MEK-ERK-MAP kinase pathway which mediates cellular response to growth signals. Somatic KRAS mutations are found at high rates in leukemia, colon cancer, pancreatic cancer and lung cancer. Studies from European and Japanese groups have recently described that activating KRAS/ BRAF mutations may play a role in the carcinogenesis of cholangiocarcinoma of the biliary tracts, but our preliminary data demonstrated low frequency of KRAS and BRAF mutation in the same tumor as well as the results from Thailand. In this study, the investigators hypothesize copy number changes rather than genetic mutation of either KRAS or BRAF genes may be the key findings of Taiwanese cases of the adenocarcinoma from the biliary tracts.

Fixed tissue in the paraffin embedded blocks

Mutation Analysis and Copy Number Changes of KRAS and BRAF Gene in Taiwanese Cases of Biliary Tact Adenocarcinoma

Far Eastern Memorial Hospital

Digestive System Diseases

Rare Diseases

Biliary Tract Neoplasms

Gallbladder Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Gallbladder Diseases

Biliary Tract Cancer

Gallbladder Cancer

Antineoplastic Agents

All Drugs and Chemicals

Capecitabine

Bevacizumab

Oxaliplatin

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Antimetabolites

There are two phases of study treatment. Phase I includes all patients and will last 6 weeks. During this phase, oxaliplatin will be given intravenously (IV) on days 1, 8, 22, and 29; bevacizumab will be given IV on days 1, 15, and 29; capecitabine will be administered orally on days 1-14 and 22-35. Radiation therapy will be given once daily for 5 days (Monday-Friday) per week for a total of 28 treatments. Phase II has two groups: 1) patients who had tumors removed prior to entering study and 2) patients who entered the study with advanced disease. Patients who had their tumors removed prior to entering the study will be treated with the above 6-week regimen twice for a total of 12 weeks of treatment. Patients who were unresectable prior to entering the study but then were deemed resectable after treatment on trial will undergo resection. Following surgical recovery (8-10 weeks) they will be treated again with the above 6-week regimen twice for a total of 12 weeks of treatment.

Given orally for 14 consecutive days (days 1-14) followed by a week of no capecitabine then another week of 14 consecutive days (days 21-28).

Given intravenously once weekly during weeks 1, 2, 4 and 5 on days 1, 8, 22 and 29

Given intravenously every two weeks during weeks 1, 3 and 5 on days 1, 15 and 29.

Once daily for 5 days (Monday through Friday) for a total of 28 treatments.

Radiation therapy

Andrew Zhu, MD

The main purpose of this study is to test the safety and effectiveness of oxaliplatin, bevacizumab, and capecitabine given in combination with radiation therapy to see what effects (good or bad) they have on patients with biliary tract and gallbladder cancer.

There are two phases of study treatment. The first phase is for all patients and will last about 6 weeks. During this phase, oxaliplatin will be given intravenously once a week during weeks 1, 2, 4, and 5 on days 1, 8, 22, and 29; bevacizumab will be given intravenously once every 2 weeks during weeks 1, 3, and 5 on days 1, 15, and 29; capecitabine will be administered orally for 14 consecutive days (days 1-14), then a week of no capecitabine, followed by another 14 days of capecitabine (days 22-35).

Radiation therapy will be given once daily for 5 days (Monday-Friday) per week for a total of 28 treatments.

During this first phase of the study the following tests will be performed weekly: physical exam, vital signs, medical history, blood tests and urine tests.

After the first phase is finished patients will wait 4 weeks then have a CT scan, MRCP, blood tests and a physical exam to evaluate the status of the disease.

Phase two of the study is broken up into two groups: 1) patients who had tumors removed prior to entering study and 2) patients who entered the study with advanced disease.

If the patients had tumors removed prior to entering the study, they will be treated again with all 3 study drugs but no radiation over a 6-week period as they did earlier in the study. This 6-week regimen will be repeated twice for a total of 12 weeks of treatment.

Patients with advanced disease that could not be removed by surgery when they first entered the study but the evaluation tests after the first phase show the tumor has responded (reduced in size) and can now be resected, will have surgery to remove the tumors.

Following surgical recovery (8-10 weeks) they will be treated again with all 3 of the study drugs but no radiation over a 6-week period as they did earlier in the study. This 6-week regimen will be repeated twice for a total of 12 weeks of study treatment.

If the evaluation tests show that the patients' cancer has remained stable (not gotten worse or better) they will be treated again with all three study drugs but no radiation over a 6-week period as they did earlier in the study. This 6-week regimen will be repeated twice for a total of 12 weeks of study treatment.

During the additional 12 weeks of study treatment a physical exam, vital signs, medical history, blood testing and urine testing will be performed once every 3 weeks.

At the end of study treatment the following evaluations will be performed: physical exam, vital signs, blood work, CT scan of the chest and abdomen, MRCP, and tumor measurements by CT scans. These evaluations will be repeated every 3 months thereafter.

Patients will be removed from the study if their disease worsens or there are unacceptable side effects.

Capecitabine, Oxaliplatin, Bevacizumab and Radiation Therapy in Patients With Biliary Tract and Gallbladder Cancer

Phase II Study of Capecitabine, Oxaliplatin, Bevacizumab and Radiation Therapy in Biliary Tract and Gallbladder Cancer

Dana-Farber Cancer Institute

Beth Israel Deaconess Medical Center

Brigham and Women's Hospital

Genentech, Inc.

Sanofi-Synthelabo

Hoffmann-La Roche

Massachusetts General Hospital

Principal Investigator

Pharmaceutical Solutions

Gemcitabine

After successful percutaneous hepatic artery cannulation, superior mesenteric arteriogram and hepatic arteriogram were performed, and after confirming that the subjects were eligible for enrollment according to the results, the hepatic artery was cannulated to the predetermined position. The catheter was connected to a syringe pump in the ward for continuous pumping of drugs.

HAIC

1000 mg/m\^2 in 100ml saline solution IV, d1, Q3W

85 mg/m\^2 in 500ml 5% glucose solution over 2 hours IV, d1, Q3W

3mg/kg (body weight \< 60kg) or 240 mg（body weight\>= 60kg）in 250 saline soluation, IV, Q3W

Toripalimab

Donafenib

This is a single center, single arm, phase II, prospective study to evaluate the efficacy and safety of Hepatic Arterial Infusion Chemotherapy (HAIC) combined with PD-1 inhibitor immunotherapy Toripalimab and Tyrosine Kinase Inhibitor Donafenib in patients with advanced biliary tract cancer.

HAIC Combined With Toripalimab and Donafenib for Advanced BTC

Phase II Study to Evaluate the Efficacy and Safety of HAIC Combined With Toripalimab and Donafenib in Patients With Advanced Biliary Tract Cancer

the sum of complete response rate and partial response rate

the sum of complete response rate, partial response rate and stable disease rate

Time from randomization to disease progression

Time from randomization to death for any cause

Unforeseen medical events occurred when the subjects received drug treatment or research, but there is not necessarily a causal relationship with the drugs used.

Severe adverse events

The concept of comprehensively evaluating the quality of life

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mutation Analysis and Copy Number Changes of KRAS and BRAF Gene in Taiwanese Cases of Biliary Tact Adenocarcinoma	NCT01588860	Biliary Tract A...		20 Years -	Far Eastern Memorial Hospital
Capecitabine, Oxaliplatin, Bevacizumab and Radiation Therapy in Patients With Biliary Tract and Gallbladder Cancer	NCT00142480	Biliary Tract C... Gallbladder Ade...	Capecitabine Oxaliplatin Bevacizumab Radiation thera...	18 Years -	Massachusetts General Hospital
Capecitabine, Oxaliplatin, Bevacizumab and Radiation Therapy in Patients With Biliary Tract and Gallbladder Cancer	NCT00142480	Biliary Tract C... Gallbladder Ade...	Capecitabine Oxaliplatin Bevacizumab Radiation thera...	18 Years -	Massachusetts General Hospital
HAIC Combined With Toripalimab and Donafenib for Advanced BTC	NCT05350943	Biliary Tract A...	HAIC Gemcitabine Oxaliplatin Toripalimab Donafenib	18 Years - 80 Years	Fudan University
HAIC Combined With Toripalimab and Donafenib for Advanced BTC	NCT05350943	Biliary Tract A...	HAIC Gemcitabine Oxaliplatin Toripalimab Donafenib	18 Years - 80 Years	Fudan University

Spots Global Cancer Trial Database for biliary tract adenocarcinoma