Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Cholangiocarcinoma

Klatskin Tumor

Disease Attributes

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Irinotecan

Antibodies

Sacituzumab govitecan

Immunoglobulins

Camptothecin

Immunoconjugates

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Patients receive sacituzumab govitecan IV over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy, PET/CT or MRI scans, and blood sample collection throughout the study.

Biopsy

Biospecimen Collection

Computed Tomography

Magnetic Resonance Imaging

Positron Emission Tomography

Sacituzumab Govitecan

Anup K. Kasi Loknath Kumar

Anup K Kasi Loknath Kumar

This phase II trial tests how well sacituzumab govitecan works in treating patients with cholangiocarcinoma that has spread to nearby tissue or lymph nodes (locally advanced), that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Sacituzumab govitecan is a monoclonal antibody, called hRS7, linked to a toxic agent, called SN-38. HRS7 is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of tumor cells, known as TROP2 receptors, and delivers SN-38 to kill them.

PRIMARY OBJECTIVE:

I. To determine anti-tumor activity by overall response rate (ORR).

SECONDARY OBJECTIVES:

I. To determine treatment safety based on toxicities participants who have received at least one dose of sacituzumab govitecan.

II. To determine anti-tumor activity by progression free survival (PFS). III. To determine anti-tumor activity by disease control rate (DCR). IV. To determine overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To determine if treatment will result in reduction of the circulating tumor deoxyribonucleic acid (DNA) as a measure of therapeutic response.

II. To determine relationship between tumor mutational profile (already performed as standard of care next generation sequencing \[NGS\] based test) to response.

OUTLINE:

Patients receive sacituzumab govitecan intravenously (IV) over 1-3 hours on days 1 and 8 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy, positron emission tomography (PET)/computed tomography (CT) or magnetic resonance imaging (MRI) scans, and blood sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days, and every 3 months for up to 24 months.

Sacituzumab Govitecan for the Treatment for Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma

A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Previously Treated Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma

Defined as best response recorded from the start of the treatment until the end of treatment (taking into account any requirement for confirmation).

Measured by computed tomography (CT) (magnetic resonance imaging \[MRI\] if CT contraindicated) Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Will be reported as a proportion with corresponding 90% confidence interval.

Measured by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

Measured by survival curve and the medical record. Will be reported using Kaplan Meier estimates of the median along with a 90% confidence interval.

National Cancer Institute (NCI)

University of Kansas Medical Center

Principal Investigator

Digestive System Diseases

Carcinoma, Ductal

Bile Duct Neoplasms

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Gastrointestinal Diseases

Gemcitabine

Cisplatin

Ricolinostat

Antimetabolites

Histone Deacetylase Inhibitors

Patients receive cisplatin IV followed by gemcitabine hydrochloride IV on days 1 and 8, and ricolinostat PO on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Gemcitabine Hydrochloride

Laboratory Biomarker Analysis

Pharmacological Study

Kabir Mody

This phase Ib trial studies the side effects and best dose of ricolinostat when given together with gemcitabine hydrochloride and cisplatin in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places in the body. Ricolinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, 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 ricolinostat together with gemcitabine hydrochloride and cisplatin may work better in treating patients with cholangiocarcinoma that cannot be removed by surgery or has spread to other places.

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) or a dose up to 240 mg/day, whichever is lower, of ricolinostat (ACY-1215) in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Cohort I)

SECONDARY OBJECTIVES:

I. Characterize the safety profile of ACY-1215 in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Both cohorts) II. Determine the single- and multiple-dose pharmacokinetic (PK) of ACY-1215 in combination with gemcitabine and cisplatin in patients with unresectable or metastatic cholangiocarcinoma. (Both cohorts) III. To evaluate tumor response to treatment with ACY-1215 in combination with gemcitabine and cisplatin (per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1 criteria). (Both cohorts) IV. To assess progression-free and overall survival of patients treated with ACY-1215 in combination with gemcitabine and cisplatin. (Both cohorts)

TERTIARY OBJECTIVES:

I. Both blood and tissue samples will be obtained at baseline and post-treatment cycle 2 for future biomarker development, analysis, and potential blood based molecular/genomic profiling. (Both cohorts) II. Studies on Tissue pre-cycle 1 and post-cycle 2 of therapy will include: phospho extracellular signal-regulated kinases (ERK)1/2; hedgehog-signaling pathways (Gli transcription factors); BIM; histones acetylation; acetylation alpha (a)-tubulin; histone deacetylase (HDAC)6 levels; autophagy markers heat shock protein (HSP)90/70; hypoxia-inducible factor 1 (HIF1)alpha; beclin; microtubule-associated proteins 1A/1B light chain 3 (LC3); Ras homolog gene family member B (RhoB).

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

Patients receive cisplatin intravenously (IV) followed by gemcitabine hydrochloride IV on days 1 and 8, and ricolinostat orally (PO) on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 1 year.

Ricolinostat, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable or Metastatic Cholangiocarcinoma

A Phase Ib, Open-Label, Dose- Escalation Trial of ACY-1215 in Combination With Gemcitabine and Cisplatin in Patients With Unresectable or Metastatic Cholangiocarcinoma

Descriptive statistics and simple scatterplots will form the basis of presentation of these data. Correlations between these laboratory values and other outcome measures like response will be carried out in an exploratory manner.

Responses will be summarized by simple descriptive summary statistics.

Will be evaluated using all cycles of treatment. Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population (overall and by tumor group). The number of responses may indicate further evaluation for specific tumor types in a Phase II setting.

Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

Mayo Clinic

Gland and Hormone Related Diseases

Pancreatic Neoplasms

Carcinoma, Hepatocellular

Gallbladder Neoplasms

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Liver Neoplasms

Liver Diseases

Gallbladder Diseases

Pancreatic Cancer

Gallbladder Cancer

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.

Van Andel Research Institute

University of Southern California

Glioblastoma

Glioma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT scan and/or MRI, as well as a tumor biopsy and blood sample collection on study.

Patricia M LoRusso

This phase II trial studies how well olaparib works in treating patients with glioma, cholangiocarcinoma, or solid tumors with IDH1 or IDH2 mutations that has spread from where it first started (primary site) to other places in the body (metastatic) and that does not respond to treatment (refractory). Olaparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVE:

I. To estimate the overall response rates of olaparib in subjects with recurrent/progressive IDH1/2-mutant solid tumors, who will be recruited to 3 cohorts: a. glioma, b. cholangiocarcinoma, c. other solid malignant tumors.

SECONDARY OBJECTIVES:

I. To estimate the distribution of progression free survival (PFS) of olaparib in adults with recurrent/progressive IDH1/2-mutant glioma and cholangiocarcinoma.

II. To estimate the overall survival (OS) in adults with recurrent/progressive IDH1/2- mutant glioma and cholangiocarcinoma.

III. To determine the duration of response in adults with recurrent/progressive IDH1/2-mutant glioma, cholangiocarcinoma or other solid malignant tumors.

IV. To confirm the safety and tolerability of olaparib monotherapy.

EXPLORATORY OBJECTIVES:

I. To describe 2HG concentration in plasma by mass spectrometry at baseline and at specific timepoints and correlate with treatment response.

II. To describe 2HG levels in tumor biopsies from prior to the beginning of treatment and at specific timepoints and correlate with treatment response.

III. To evaluate in tumor biopsies and in liquid biopsies performed at baseline and at specific timepoints if co-occurring alterations detected via multiplexed immunofluorescence, mass cytometry (CyTOF)-imaging mass cytometry (IMC), ribonucleic acid (RNA) sequencing and/or deoxyribonucleic acid (DNA) sequencing can be associated with differential levels of 2HG production, treatment response and resistance.

OUTLINE:

Patients receive olaparib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a computer tomography (CT) scan and/or magnetic resonance imaging (MRI), as well as a tumor biopsy and blood sample collection on study.

After completion of study treatment, patients are followed up for 30 days.

Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations

A Phase 2 Study of the PARP Inhibitor Olaparib (AZD2281) in IDH1 and IDH2 Mutant Advanced Solid Tumors

Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically versus (vs.) time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Will be detected via mass cytometry, ribonucleic acid sequencing and/or deoxyribonucleic acid sequencing. Will be associated with differential levels of 2HG production, treatment response and resistance. Absolute and fold changes for exploratory endpoints will be calculated between baseline and each subsequent follow-up time point. These will be displayed graphically vs. time for each cohort. Differences will be plotted vs. response status. Paired t-tests will be used to evaluate if differences between baseline and each subsequent time point are significant. Summary statistics will be reported (with 95% confidence intervals) to demonstrate mean differences in fold-change (or log fold-change) between responders and non-responders.

Will be determined by investigator assessment using Response Evaluation Criteria in Solid Tumors version 1.1 for extracranial solid tumors, Response Assessment in Neuro-Oncology criteria for intracranial glioma. Overall response rate and a 90% creditable interval in each cohort will be estimated using the approach described by Koyama. For the other solid tumors cohort, descriptive statistics and graphical displays will be used to summarize results within tumor types.

For time to event endpoints, Kaplan-Meier curves will be used to demonstrate distributions and median estimates will be reported with 95% confidence intervals. For each cohort, graphical displays such as swimmer plots, will be used to demonstrate patterns of response, progression and death, and in the third cohort they will also indicate disease type.

Adverse events will be tabulated by type and grade in each cohort, and also across cohorts.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sacituzumab Govitecan for the Treatment for Patients With Locally Advanced, Recurrent, or Metastatic Cholangiocarcinoma	NCT06178588	Locally Advance... Metastatic Chol... Recurrent Chola... Stage III Hilar... Stage III Intra... Stage IV Hilar ... Stage IV Intrah...	Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Positron Emissi... Sacituzumab Gov...	18 Years -	University of Kansas Medical Center
Ricolinostat, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable or Metastatic Cholangiocarcinoma	NCT02856568	Non-Resectable ... Recurrent Chola... Stage III Extra... Stage III Intra... Stage IIIA Hila... Stage IIIB Hila... Stage IVA Extra... Stage IVA Hilar... Stage IVA Intra... Stage IVB Extra... Stage IVB Hilar... Stage IVB Intra... Unresectable Ex...	Cisplatin Gemcitabine Hyd... Laboratory Biom... Pharmacological... Ricolinostat	18 Years -	Mayo Clinic
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
Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations	NCT03212274	Advanced Malign... Glioblastoma Recurrent Chola... Recurrent Gliom... Recurrent Malig... WHO Grade 2 Gli... WHO Grade 3 Gli...	Biopsy Biospecimen Col... Computed Tomogr... Magnetic Resona... Olaparib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for recurrent cholangiocarcinoma