Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Cholangiocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Bile Duct Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Immunomodulating Agents

Nivolumab

Immunoglobulins

Entinostat

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Histone Deacetylase Inhibitors

Enzyme Inhibitors

Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle).

After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Nilofer Azad, MD

The proposed study is an open-label, two-arm study of entinostat plus nivolumab in patients with unresectable or metastatic cholangiocarcinoma (CCA) or pancreatic ductal adenocarcinoma (PDAC).

A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma

A Phase 2 Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma

Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions. Subjects who discontinue due to clinical progression prior to post-baseline tumor assessments were considered as non-responders.

When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.

OS is defined as the duration of time from start of study treatment to time of death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

OS is defined as the proportion of subjects who are alive at 6 months. Estimation based on the Kaplan-Meier curve.

OS is defined as the proportion of subjects who are alive at 12 months. Estimation based on the Kaplan-Meier curve.

OS is defined as the proportion of subjects who are alive at 24 months. Estimation based on the Kaplan-Meier curve.

OS is defined as the proportion of subjects who are alive at 36 months. Estimation based on the Kaplan-Meier curve.

Duration of response (DOR) will be calculated for subjects who achieve a best overall response of CR or PR. DOR is defined as the number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions.

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 6 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 12 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 24 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

Syndax Pharmaceuticals

Bristol-Myers Squibb

National Cancer Institute (NCI)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements.

Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle).

Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Arm A - Cholangiocarcinoma

ARM B - Pancreatic Cancer

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)

Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)

Overall Survival (OS)

Overall Survival (OS) at 6 Months

Overall Survival (OS) at 12 Months

Overall Survival (OS) at 24 Months

Overall Survival (OS) at 36 Months

There were no responses (PR or CR) observed in Arm A; therefore, the number of analyzed participants is zero. 3 participants achieved response in Arm B.

Duration of Response (DOR)

Progression Free Survival (PFS) at 6 Months

Progression Free Survival (PFS) at 12 Months

Progression Free Survival (PFS) at 24 Months

Overall Study

Gemcitabine

Cisplatin

Ivosidenib

Antimetabolites

Patients receive ivosidenib PO on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive pemigatinib PO on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Pemigatinib

Shubham Pant

This phase I trial studies the side effects and best dose of gemcitabine and cisplatin when given together with ivosidenib or pemigatinib in treating patients with cholangiocarcinoma that cannot be removed with surgery (unresectable) or has spread to other places in the body (metastatic). Chemotherapy drugs, such as gemcitabine 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. Ivosidenib and pemigatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine and cisplatin with ivosidenib or pemigatinib may work better in treating patients with cholangiocarcinoma compared to gemcitabine and cisplatin alone.

PRIMARY OBJECTIVE:

I. To evaluate the safety, tolerability, maximum tolerated dose (MTD) and/or recommended phase 2 dose, gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib.

SECONDARY OBJECTIVES:

I. To evaluate median and progression free survival (PFS) for 6 months per investigator assessment.

II. To evaluate the rate of overall survival (OS) in patients treated with gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib.

III. To describe the overall toxicity and adverse events profile associated with gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib.

IV. To determine the best response profile per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients treated with gemcitabine and cisplatin in combination with either ivosidenib or pemigatinib.

CORRELATIVE RESEARCH OBJECTIVE:

I. To measure plasma 2-hydroxglutarate (2-HG) levels =\< 21 days prior to registration and at cycle 4 day 1 (+/- 2 days).

OUTLINE: This is a dose de-escalation study. Patients are assigned to 1 of 2 arms.

ARM A (IDH1 GENE MUTATION): Patients receive ivosidenib orally (PO) on days 1-21, cisplatin intravenously (IV) on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B (FGFR2 GENE ALTERATION): Patients receive pemigatinib PO on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles 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 6 months for up to 3 years.

Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma

A Phase I, Multi-Center, Open Label, Dose De-Escalation and Expansion Study of Gemcitabine and Cisplatin With AG120 or Pemigatinib for Advanced Cholangiocarcinoma

A significant toxicity is defined as a Dose Limiting Toxicity that is possibly, probably, or definitely related to treatment. DLTs will be evaluated starting in the first cycle of combination treatment and up to 3 weeks of combination treatment. Toxicities will be assessed using the CTEP Active Version of the CTCAE. All patients meeting the eligibility criteria who have signed a consent form and have begun combination treatment will be considered evaluable for significant toxicity. Patients, who do not experience a DLT but withdraw from protocol therapy prior to 3 weeks, will not be evaluable for the primary endpoint. Incidence of significant toxicity at 3 weeks will be estimated separately by arm and will be defined as the number of patients with significant toxicity within 3 weeks of combination treatment divided by the total number of evaluable patients.

Overall survival is defined to be the length of time from start of study therapy to death due to any cause. All patients meeting the eligibility criteria that have signed a consent form and begun treatment will be considered evaluable for estimation of the survival distribution. The distribution of overall survival for both arms of the study will be estimated separately using the Kaplan-Meier method.

Progression free survival time is defined as the time from the start of study therapy to documentation of disease progression. Patients who die without documentation of progression will be considered to have had tumor progression at the time of death. Patients who are still alive and have not progressed will be censored for progression at the time of the last disease evaluation. The time-to-progression distribution will be estimated separately for both arms, using the Kaplan-Meier method.

The number and severity of all adverse events (overall, by dose-level, and by tumor group) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion.

The term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. 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.

Best Response is defined to be the best objective status recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response Evaluation Criteria in Solid Tumors 1.1 criteria will be used for tumor evaluation and patients will be re-evaluated every prior to treatment in cycle 3 and then in odd subsequent cycles. 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).

Academic and Community Cancer Research United

Arm A patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm A (Ivosidenib, Cisplatin, Gemcitabine)

Arm B patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm B (Pemigatinib, Cisplatin, Gemcitabine)

Arm A patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Arm B patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm A (Ivosidenib, Cisplatin, Gemcitabine) and Arm B (Pemigatinib, Cisplatin, Gemcitabine)

Age, Continuous

Primary Tumor Site

Arms A and B are reported together to maintain patient deidentification and privacy.

Patients receive ivosidenib PO at a starting dose of 500mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive pemigatinib PO at a starting dose of 13.5mg on days 1-21, cisplatin IV on days 1 and 8, and gemcitabine IV on days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm B (Pemigatinib, Gemcitabine, Cisplatin)

Only patients that completed cycle 1 treatment per protocol were evaluated.

Number of Participants With Significant Toxicities

B (Pemigatinib, Cisplatin, Gemcitabine)

Overall Survival

Progression Free Survival

Number of Patients Experiencing Adverse Events

Number of Participants Experiencing Toxicities

Best Response

Carcinoma, Hepatocellular

Liver Neoplasms

Liver Diseases

Intrahepatic Cholangiocarcinoma

Hematinics

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Liver Extracts

Pevonedistat

Tubulin Modulators

Antimitotic Agents

Patients receive pevonedistat IV over 60 minutes on days 1, 3, and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients receive pevonedistat IV over 1 hour on days 1, 3, and 5, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 15-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Starting cycle 5, patients may receive pevonedistat monotherapy at the discretion of treating physician.

Dustin A Deming

This phase II trial studies how well pevonedistat alone or in combination with chemotherapy (paclitaxel and carboplatin) works in treating patients with bile duct cancer of the liver. Pevonedistat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as paclitaxel and carboplatin, 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. This study may help the study doctors find out how well pevonedistat shrinks bile duct cancer of the liver when given alone and when in combination with paclitaxel and carboplatin.

PRIMARY OBJECTIVE:

I. To determine the objective response rate of pevonedistat as a single agent and in combination with carboplatin and paclitaxel in patients with unresectable intrahepatic cholangiocarcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the safety profile of pevonedistat alone and in combination with carboplatin and paclitaxel in patients with intrahepatic cholangiocarcinoma.

II. To determine the clinical benefit rate of patients with advanced intrahepatic cholangiocarcinoma (ICC) treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel.

III. To determine progression-free survival of patients treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel.

IV. To determine overall survival of patients treated with pevonedistat monotherapy and in combination with carboplatin and paclitaxel.

EXPLORATORY OBJECTIVES:

I. To determine whether overexpression of NEDD8, NAE1, and UBC12 predict response to treatment.

II. To identify the mutation profile of those cholangiocarcinomas with overexpression of the neddylation pathway.

III. To bank specimens for further future investigations.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive pevonedistat intravenously (IV) over 60 minutes on days 1, 3, and 5. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive pevonedistat IV over 1 hour on days 1, 3, and 5, paclitaxel IV over 3 hours on day 1, and carboplatin IV over 15-60 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Starting cycle 5, patients may receive pevonedistat monotherapy at the discretion of treating physician.

After completion of study treatment, patients are followed up at 30 days after last dose of study treatment, then every 3 months for the first year and every 6 months for years 2-3.

Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver

A Phase 2 Study of Pevonedistat in Combination With Carboplatin and Paclitaxel in Advanced Intrahepatic Cholangiocarcinoma

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will perform immunohistochemistry on formalin-fixed paraffin-embedded (FFPE) tissue determine whether overexpression of NEDD8, NAE1, and UBC12 can predict response to treatment. Biomarker quantification will be calculated as a continuous variable (mean optical density) and also as ordered categories (ex. 0, 1+, 2+, or 3+). Biomarker quantification will then be correlated with treatment response. Descriptive statistics will primarily be generated to summarize the correlative data. Statistical significance will be determined by students' t-test for normally distributed data. If data distributions are not normal, non-parametric methods will be used (Wilcoxon rank sum test).

Will assess complete or partial response by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Mitogens

Participants who experience disease progression while receiving gemcitabine + cisplatin or during the follow-up period and before starting a new anticancer therapy will be eligible to cross over and receive pemigatinib.

Pemigatinib at the protocol-defined dose administered orally once daily as continuous therapy schedule (a cycle is 3 weeks).

Gemcitabine 1000 mg/m\^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.

Cisplatin 25 mg/m\^2 administered as an intravenous infusion on Days 1 and 8 of every 3-week cycle for up to 8 cycles.

Incyte Corporation Call Center (US)

Incyte Corporation Call Center (ex-US)

Study Coordinator

Peter Langmuir, MD

The purpose of this study is to evaluate the efficacy and safety of pemigatinib versus gemcitabine plus cisplatin chemotherapy in first-line treatment of participants with unresectable or metastatic cholangiocarcinoma with FGFR2 rearrangement.

A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma

A Phase 3, Open-Label, Randomized, Active-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Gemcitabine Plus Cisplatin Chemotherapy in First-Line Treatment of Participants With Unresectable or Metastatic Cholangiocarcinoma With FGFR2 Rearrangement (FIGHT-302)

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Defined as the time from date of randomization until date of disease progression (according to Response Evaluation Criteria in Solid Tumors \[RECIST\] v1.1 and assessed by an independent central reviewer (ICR)) or death, whichever occurs first.

Defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 as assessed by an ICR.

Defined as the time from date of randomization until death due to any cause.

Defined as the time from the date of the first assessment of CR or PR until the date of the first disease progression by an ICR per RECIST v1.1 or death, whichever occurs first.

Defined as the proportion of participants who achieved best overall response of CR, PR, or stable disease (SD) per RECIST v1.1 as assessed by an ICR.

Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug.

Incyte Corporation

Klatskin Tumor

Capecitabine

Patients with unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases

Patients will receive neoadjuvant radiotherapy (External - 50-54 grays) following by concomitant oral capecitabine (825mg/m2 bid).Thereafter, gemcitabine iv (1000mg/m2) plus cisplatin iv (25mg/m2) will be administered the day 1 and 8 every 21 days until transplant.

Neoadjuvant Chemo-radiotherapy

If no spread disease is discovered after neoadjuvant treatment, the patient will be listed for liver transplantation.

Liver Transplantation

CRISTINA DOPAZO, MD/PhD

Cristina Dopazo, PhD/MD

Cristina Dopazo

Ramón Charco-Torra

Sonia Pascual-Bartolomé

Carmelo Loinaz-Segurola

José María Álamo-Martinez

José Luis Lucena de la Poza

Arturo Colon-Rodríguez

Diego López-Segarra

Yilliam Fundora-Suárez

Andrea Bosca-Robledo

Juan Andrés Echeverri-Cifuentes

Josefina López-Domínguez

Xavier Merino-Casabiel

David Leiva-Pedraza

María Teresa Salcedo-Allende

José Antonio Gracia Solanas

Manuel Angel Barrera-Gómez

Ricardo Robles-Campos

Laura Lladó-Garrida

María Teresa Macarulla-Mercadé

Begoña Navalpotro-Yagüe

Florian Castet

Julio Santoyo

Manuel Durán Martínez

Natalia Zambudio

A prospective multicentre study which includes patients ≤ 70 years-old diagnosed of unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases. Liver transplantation preceded by neoadjuvant radio-chemotherapy will be performed in this selected group.

The primary endpoint will be overall survival at 1, 3, and 5 years post-transplant. The secondary endpoints will be: 1) recurrence free survival at 1, 3 and 5 years post-transplant; 2) intention-to-treat survival of overall patients included in the study at 1,3 and 5 year; 3) the rate of patients included in the study who are finally transplanted.

A prospective multicentre pilot study which includes patients ≤ 70 years-old diagnosed of unresectable hilar cholangiocarcinoma (hCCA) ≤3cm in radial diameter, without evidence of lymph node or distant metastases.

The number of subjects necessary is 34 patients to achieve a power of 82% with a significance level of 0.05 to detect a 40% difference between the estimated 50% survival of those patients who are transplanted and 10% of those patients with hCCA unresectable who are not transplanted. This corresponds to a hazard ratio of 3.3219. Estimated loss to follow-up of 10% of patients.

RADIOLOGICAL EVALUATION

It will be considered unresectable those lesions Bismuth IV with the following criteria (Jarnagin WR, et al. Ann Surg 2001; 234:507; Memorial Sloan Kettering Cancer Center Hilar Cholangiocarcinoma Classification):

* Bilateral extension to second order biliary
* Unilateral extension to second-order biliary radicals AND contralateral portal vein involvement OR contralateral hepatic lobar atrophy
* Main or bilateral portal vein involvement
* Insufficient future liver remnant even after portal embolization

It will be performed the tumoral marker (CA 19.9), multiphase chest-abdomen CT scan, magnetic resonance cholangiopancreatography (MRCP) as well as positon emission tomography (PET)-scan if there is doubts of distant disease and upper endoscopic ultrasound (EUS) in order to rule out any obvious lymph node metastases. A biliary drainage will be placed by percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD).

NEOADJUVANT TREATMENT

Patients will receive neoadjuvant radiotherapy (External - 50-54 grays) following by concomitant oral capecitabine (1,330mg/m2).Thereafter, gemcitabine iv (1000mg/m2) plus cisplatin iv will be administered the day 1 and 8 every 21 days until transplant.

A staging laparotomy/laparoscopy is recommended before including the patient in waiting list for transplant to confirm the abscence of extra-hepatic disease, especially peritoneal seeding and lymph nodes involvement.

A score exception will be allowed to optimized the treatment received and to be transplanted during the first 6 months.

LIVER TRANSPLANT AND FOLLOW UP

Regarding liver transplant technique, hepatic artery should be avoided for arterial reconstruction using the splenic artery or an iliac conduit.

Biomarker analyses in the explant specimen will be performed.

The patient will be monitored post-operatively at the clinical, biological and morphological levels every 3 months during the first 2 years and every 6 months thereafter in order to detect any recurrence and in the context of standard clinical care.

Liver Transplant Combined With Neoadjuvant Chemo-radiotherapy in the Treatment of Unresectable Hilar Cholangiocarcinoma. A Prospective Multicenter Study.

Hospital Vall d'Hebron

Consultant Surgeon

Crouzon Syndrome

Jackson-Weiss Syndrome

Pfeiffer Syndrome

Participants will receive E7090 140 mg (milligram), tablets orally once daily (QD), in 28-days treatment cycle until disease progression, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination.

E7090

The primary purpose of the study is to assess the objective response rate (ORR) of E7090 by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 based on independent imaging review (IIR) in participants with unresectable cholangiocarcinoma with FGFR2 gene fusion who failed gemcitabine-based combination chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma	NCT03250273	Metastatic Chol... Cholangiocarcin... Pancreatic Canc... Metastatic Panc... Unresectable Pa... Unresectable Ch...	Entinostat Nivolumab Entinostat Nivolumab	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Gemcitabine and Cisplatin With Ivosidenib or Pemigatinib for the Treatment of Unresectable or Metastatic Cholangiocarcinoma	NCT04088188	Advanced Cholan... Metastatic Chol... Unresectable Ch...	Cisplatin Gemcitabine Ivosidenib Pemigatinib	18 Years -	Academic and Community Cancer Research United
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver	NCT04175912	Metastatic Chol... Metastatic Hepa... Stage III Hepat... Stage III Intra... Stage IIIA Hepa... Stage IIIA Intr... Stage IIIB Hepa... Stage IIIB Intr... Stage IV Hepato... Stage IV Intrah... Stage IVA Hepat... Stage IVB Hepat... Unresectable Ch... Unresectable He... Unresectable In...	Carboplatin Paclitaxel Pevonedistat	18 Years -	National Cancer Institute (NCI)
A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma	NCT03656536	Unresectable Ch... Metastatic Chol...	Pemigatinib Gemcitabine Cisplatin	18 Years -	Incyte Corporation
A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma	NCT03656536	Unresectable Ch... Metastatic Chol...	Pemigatinib Gemcitabine Cisplatin	18 Years -	Incyte Corporation
Liver Transplant Combined With Neoadjuvant Chemo-radiotherapy in the Treatment of Unresectable Hilar Cholangiocarcinoma. A Prospective Multicenter Study.	NCT04378023	Unresectable Ch...	Neoadjuvant Che... Liver Transplan...	18 Years - 70 Years	Hospital Vall d'Hebron
A Study of E7090 in Participants With Unresectable Advanced or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor (FGFR) 2 Gene Fusion	NCT04238715	Cholangiocarcin...	E7090	20 Years -	Eisai Inc.

Spots Global Cancer Trial Database for unresectable cholangiocarcinoma