Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Carcinoma

Cholangiocarcinoma

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma, Hepatocellular

Carcinoma, Ductal

Gallbladder Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Liver Neoplasms

Liver Diseases

Biliary Tract Neoplasms

Biliary Tract Diseases

Gallbladder Diseases

Pancreatic Cancer

Bile Duct Cancer

Gallbladder Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Hematinics

Durvalumab

Liver Extracts

Guadecitabine

Antineoplastic Agents, Immunological

Patients receive guadecitabine SC QD on days 1-5 and durvalumab IV over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Anthony El-Khoueiry, MD

This phase Ib trial studies the side effects and best dose of guadecitabine and how well it works when given together with durvalumab in treating patients with liver, pancreatic, bile duct, or gallbladder cancer that has spread to other places in the body. Guadecitabine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as durvalumab, may block tumor growth in different ways by targeting certain cells. Giving guadecitabine and durvalumab may work better in treating patients with liver, pancreatic, bile duct, or gallbladder cancer.

PRIMARY OBJECTIVES:

I. To evaluate the dose limiting toxicities and determine the maximum tolerated dose/recommended phase 2 dose of the combination of guadecitabine and durvalumab. (Dose escalation part) II. To evaluate the objective response rate (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) for the combination of guadecitabine and durvalumab in hepatocellular carcinoma, pancreatic cancer and cholangiocarcinoma cohorts, respectively. (Expansion part)

SECONDARY OBJECTIVES:

I. To describe the safety and tolerability of the combination of guadecitabine and durvalumab.

II. To estimate the progression-free and overall survival of patients with advanced hepatocellular carcinoma (HCC), pancreatic cancer and biliary cancers treated with the combination of guadecitabine and durvalumab.

TERTIARY OBJECTIVES:

I. Correlate programmed cell death ligand 1 (PD-L1) and programmed cell death protein 1 (PD1) expression on various cells within tumor samples and anti-tumor effect (response rate and survival).

II. Correlate effector T cells (Teff)/regulatory T cells (Treg) ratio in the tumor and anti-tumor effect.

III. Correlate granulocytic and monocytic myeloid-derived suppressor cells (MDSCs) level in the peripheral blood using fluorescence-activated cell sorting (FACS) and anti-tumor effect.

IV. Evaluate changes in inflammatory T cell signatures pre and post treatment and potential associations with anti-tumor effect.

V. Assess the induction, activation, expansion and tumor infiltration of tumor neo-epitope-specific T cells.

VI. Explore changes in gene methylation and expression with anti-tumor effect, with particular emphasis on the ancestry-informative marker (AIM) gene panel.

VII. Correlate immunologic changes in pre- and post-treatment peripheral blood mononuclear cell (PBMCs) and anti-tumor effect.

OUTLINE: This is a dose-escalation study of guadecitabine.

Patients receive guadecitabine subcutaneously (SC) once daily (QD) on days 1-5 and durvalumab intravenously (IV) over 60 minutes on day 8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months.

Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer

A Phase Ib Study of Guadecitabine (SGI-110) and Durvalumab (MEDI 4736) in Patients With Advanced Hepatocellular Carcinoma, Pancreatic Adenocarcinoma, and Cholangiocarcinoma/Gallbladder Cancer

Graded according to Common Terminology Criteria for Adverse Events version 4.03.

Will be calculated by the percentage of patients having complete or partial response among all patients who have been treated at maximum tolerated dose/recommended phase II dose in each cohort. Will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST).

Kaplan-Meier curves will be used to show overall survival in each cohort. Median overall survival and 95% confidence intervals will be derived from Kaplan-Meier curves.

Kaplan-Meier curves will be used to show progression-free survival in each cohort. Median progression-free survival and 95% confidence intervals will be derived from Kaplan-Meier curves.

National Cancer Institute (NCI)

Van Andel Research Institute

University of Southern California

Biliary Tract Cancer

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Ramucirumab

Lexatumumab

Immunoglobulins, Intravenous

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive ramucirumab IV over 60 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

Laboratory Biomarker Analysis

Rachna T Shroff

This phase II trial studies how well ramucirumab works in treating patients with previously treated biliary cancers that have spread to other places in the body and usually cannot be cured or controlled with treatment (advanced) or have spread to other places in the body (metastatic) and cannot be removed by surgery. Immunotherapy with monoclonal antibodies, such as ramucirumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

PRIMARY OBJECTIVES:

I. Determine the progression-free survival (PFS) of ramucirumab in advanced biliary cancers (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer) who have received prior chemotherapy.

SECONDARY OBJECTIVES:

I. Determine the response rate (RR) and disease control rate (partial response + complete response + stable disease) of ramucirumab in advanced biliary cancers.

II. Determine overall survival (OS) of ramucirumab in advanced biliary cancers. III. Evaluate the toxicity of ramucirumab in advanced biliary cancers.

EXPLORATORY OBJECTIVES:

I. Correlate the carbohydrate antigen (CA) 19-9 response (defined as \> 50% decrease from baseline) with tumor response, PFS and OS.

II. Correlate baseline tumor gene expression profile with PFS. III. Correlate pre- and post-therapy computed tomography (CT) imaging to quantify iodine content, atomic numbers, and Z-values and correlate with response.

OUTLINE:

Patients receive ramucirumab intravenously (IV) over 60 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Ramucirumab in Treating Patients With Advanced or Metastatic, Previously Treated Biliary Cancers That Cannot Be Removed by Surgery

A Phase II Study of Ramucirumab for Advanced, Pre-Treated Biliary Cancers

Progression free survival is measured using 95% confidence intervals. From the date of treatment start to the date of disease progression or to the date of death, whichever occurs first, or to the last follow-up date if patients are alive without disease progression, assessed up to at least 3 months post-treatment

Overal Survival (OS): the time from treatment initiation to death from any cause. OS functions were estimated using the Kaplan-Meier method .

The proportion of patients with the best overall response of complete response or partial response (PR)\]

Partial Response + Complete Response + Stable Disease (ORR + Stable Disease)

M.D. Anderson Cancer Center

Phase II, single-arm trial for advanced, unresectable, pre-treated patients with BTC. Eligible patients received ramucirumab 8 mg/kg IV on day 1 of a 14-day cycle until progression or intolerable toxicity.

Phase II Open-label, Single Arm Study of Ramucirumab Administered at 8 mg/kg IV.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Milind Javle

Progression Free Survival of Ramucirumab in Advanced Biliary Cancers

Phase II, single-arm trial for advanced, unresectable, pre-treated patients with BTC with ECOG 0/1, adequate liver, renal, and marrow functions

Overall Survival (OS)

Phase II Open-label, Single Arm Study of Ramucirumab Administered at 8 mg/kg IV

Overall Response Rate (RR)

Percentage of Disease Control Rate

Overall Study

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine Hydrochloride

Nab-paclitaxel

This phase II trial studies how well gemcitabine hydrochloride, cisplatin, and nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation) work in treating patients with biliary cancers (which includes the gallbladder and bile ducts inside and outside the liver) that have spread to other places in the body and usually cannot be cured or controlled with treatment. Drugs used in chemotherapy, such as gemcitabine hydrochloride, cisplatin, and paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine the progression-free survival (PFS) of gemcitabine hydrochloride (gemcitabine), cisplatin, and nab-paclitaxel in advanced, untreated biliary cancers (intrahepatic cholangiocarcinomas, extrahepatic cholangiocarcinomas, and gallbladder cancers).

SECONDARY OBJECTIVES:

I. Determine the response rate (RR) and disease control rate (partial response + complete response + stable disease) of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers.

II. Determine overall survival (OS) of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers.

III. Evaluate the toxicity of gemcitabine, cisplatin, and nab-paclitaxel in advanced biliary cancers.

EXPLORATORY OBJECTIVES:

I. Correlate the carbohydrate antigen (CA) 19-9 response (defined as \>50% decrease from baseline) with tumor response, PFS and OS.

II. Assess ribonucleotide reductase subunit MI (RRMI), excision repair cross-complementation group 1 (ERCC1) pre-treatment status and correlate with tumor response, PFS and OS on an exploratory basis.

III. Collect optional blood and tissue at the start of treatment and at progression to explore mechanisms of resistance.

OUTLINE:

Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) over 30 minutes, cisplatin IV over 60 minutes, and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months thereafter.

Gemcitabine Hydrochloride, Cisplatin, and Nab-Paclitaxel in Treating Patients With Advanced or Metastatic Biliary Cancers

A Phase II Study of Gemcitabine, Cisplatin, and Abraxane in Advanced Biliary Cancers

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

The Kaplan-Meier method was used to estimate OS, with surviving patients censored at the time of surgery or at last known follow-up.

Per Response Evaluation Criteria In Solid Tumors Criteria(RECIST v1.1.14) for target lesions and assessed by MRI: Complete Response (CR),Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Gemcitabine 1000mg/m2, Cisplatin 25mg/m2 \& Nab-Paclitaxel 125mg/m2 on days 1 \& 8 of a 21 day cycle.

High Dose

Gemcitabine 800mg/m2, Cisplatin 25mg/m2 \& Nab-Paclitaxel 100mg/m2 on days 1 \& 8 of a 21 day cycle.

Low Dose

High Dosage

Low Dosage

Total

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Intrahepatic cholangiocarcinoma (IHCC)

Extrahepatic cholangiocarcinoma (EHCC)

Gallbladder Cancer (GBC)

Tumor Type

Dr. Milind Javle, Professor, GI Medical Oncology

Gemcitabine 1000mg/m2, Cisplatin 25mg/m2 \& Nab-Paclitaxel 125mg/m2 on days 1 \& 8 of a 21 day cycle

3 participants are not included due to 2 Discontinued during cycle 1 (adverse event) and 1 Refused treatment following cycle 1 (patient choice). The analysis for PFS were calculated for the total treated population that received both high and low dosage.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Guadecitabine and Durvalumab in Treating Patients With Advanced Liver, Pancreatic, Bile Duct, or Gallbladder Cancer	NCT03257761	Extrahepatic Bi... Gallbladder Ade... Metastatic Panc... Recurrent Chola... Recurrent Gallb... Recurrent Hepat... Recurrent Intra... Recurrent Pancr... Stage III Gallb... Stage III Hepat... Stage III Intra... Stage III Pancr... Stage IIIA Gall... Stage IIIA Hepa... Stage IIIB Gall... Stage IIIB Hepa... Stage IIIC Hepa... Stage IV Gallbl... Stage IV Hepato... Stage IV Pancre... Stage IVA Gallb... Stage IVA Hepat... Stage IVA Intra... Stage IVB Gallb... Stage IVB Hepat... Stage IVB Intra... Unresectable Ga... Unresectable Pa...	Durvalumab Guadecitabine	18 Years -	University of Southern California
Ramucirumab in Treating Patients With Advanced or Metastatic, Previously Treated Biliary Cancers That Cannot Be Removed by Surgery	NCT02520141	Cholangiocarcin... Liver and Intra... Stage III Gallb... Stage III Intra... Stage IIIA Gall... Stage IIIB Gall... Stage IV Gallbl... Stage IVA Gallb... Stage IVA Intra... Stage IVB Gallb... Stage IVB Intra... Unresectable Ga...	Laboratory Biom... Ramucirumab	18 Years -	M.D. Anderson Cancer Center
Gemcitabine Hydrochloride, Cisplatin, and Nab-Paclitaxel in Treating Patients With Advanced or Metastatic Biliary Cancers	NCT02392637	Stage III Intra... Stage IIIA Gall... Stage IIIB Gall... Stage IVA Gallb... Stage IVA Intra... Stage IVB Gallb... Stage IVB Intra... Unresectable Ex... Unresectable Ga...	Cisplatin Gemcitabine Hyd... Laboratory Biom... Nab-paclitaxel	18 Years -	M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for stage ivb intrahepatic cholangiocarcinoma ajcc v7