Neoplasms

All Conditions

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Antineoplastic Agents

All Drugs and Chemicals

Ivosidenib

Enzyme Inhibitors

Subjects will take 2 tablets (500 mg total) orally once daily.

This study will enroll participants with nonresectable or metastatic cholangiocarcinoma with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have previously received at least 1, but no more than 2, prior regimens for advanced disease. All participants will receive ivosidenib daily throughout multiple 28 day cycles. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), every other week during Cycles 2 and 3, and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an end of treatment and a post-treatment follow-up visit, and participants will be followed to assess overall survival. Study visits may include a tumor assessment, physical exam, electrocardiogram (ECG), blood and urine analysis, and questionnaires.

A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

A Phase 2, Open-label, Multicenter Study of Orally Administered Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

* used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Proportion of subjects who are alive and progression-free (using RECIST v1.1) at 6 months after Day 1 (C1D1) per Independent Radiology Center (IRC)

The time from Day 1 to the date of first documentation of disease progression as assessed by the Investigator and by the IRC per RECIST v1.1. or death due to any cause

The time from date of first documented confirmed complete response (CR) or confirmed partial response (PR) to date of first documented disease progression or death due to any cause

The time from Day 1 to date of first documented confirmed complete response (CR) or confirmed partial response (PR)

The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30) scores range from 0 - 100 and asses both functional scores and symptom scores; for the functional score the higher score represents better functioning and for the symptom scores the higher score represents an increase in symptoms.

The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (EORTC-QLQ-BIL21) scores range from 0 - 100 with higher scores representing more severe symptoms.

The 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) scores range from 5 to 25 with a higher number representing a worse health status.

From baseline to worst value of post-baseline assessments. ECOG PS scores range from 0 to 5 with 0 representing a person being fully active and 5 being the patient is dead.

Servier

Gallbladder Cancer

Micronutrients

Hematinics

Vitamins

Gemcitabine

Leucovorin

Fluorouracil

Irinotecan

Antidotes

Protective Agents

Folic Acid

Vitamin B Complex

Trace Elements

Folate

Vitamin B9

nal-IRI \[Irinotecan liposome\] (80 mg/m2 as a 1.5 hour infusion), 5-FU \[5-Fluorouracil\] (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)

Control intervention/standard arm: 5-FU (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)

nal-IRI \[Irinotecan liposome\] (80 mg/m2 as a 1.5 hour infusion)

nal-IRI

5-FU \[5-Fluorouracil\] (2400 mg/m2 as 46 hour infusion)

5-FU

leucovorin (400 mg/m2 as 0.5 hour infusion)

leucovorin

Arndt Vogel, Prof.

is an open label, randomized, multicenter phase II trial

The primary objective is to assess the efficacy of nal-IRI in gemcitabine pre-treated patients with advanced, unresectable and metastatic cholangio- and gallbladder carcinoma eligible for treatments after failure to respond to a gemcitabine-based treatment

Nal-IRI and 5-FU Compared to 5-FU in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies

A Randomized Phase II Trial of Nal-IRI and 5-Fluorouracil Compared to 5-Fluorouracil in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies

will be collected to potentially identify factors that may correlate with tumour response, sensitivity or resistance to nal-IRI

Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

according to Common Terminology Criteria for Adverse Events

AIO-Studien-gGmbH

Digestive System Diseases

Bile Duct Neoplasms

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Gastrointestinal Diseases

Intrahepatic Cholangiocarcinoma

Cisplatin

Immunomodulating Agents

Durvalumab

Antimetabolites

Antineoplastic Agents, Immunological

Participants will receive:

* Cycle 1:

Day 1 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy) plus Durvalumab (immunotherapy).

Day 8 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy)

Week 2 or 3 of 21 Day Cycle: One time treatment of Y-90 radiation.

* Cycles 2-8:

Day 1 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy) plus Durvalumab (immunotherapy).

Day 8 of 21 Day cycle: Pre-determined dose(s) of Gemcitabine and Cisplatin (Chemotherapy)

* Cycles 9+:

Day 1 of 21 Day Cycle: Durvalumab (immunotherapy) maintenance

Yttrium-90

Andrea Bullock, MD, MPH

Victoria Weden, BS

This trial is designed to study a combination of interventions (chemotherapy, immunotherapy, and radiation) as a potential new treatment for bile duct cancer that cannot be removed with surgery.

The specific names of the interventions that will be used are:

* Y-90 (a type of radiation microsphere bead)
* Durvalumab (a type of immunotherapy)
* Gemcitabine (a type of chemotherapy)
* Cisplatin (a type of chemotherapy)

This is a single arm Phase II, non-randomized, open-label clinical trial assessing the safety and efficacy of Y-90 SIRT in combination with durvalumab, gemcitabine and cisplatin in participants with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma.

The U.S. Food and Drug Administration (FDA) has approved durvalumab for bile duct cancer that cannot be removed with surgery, but it has been approved for other uses.

The U.S. Food and Drug Administration (FDA) has already approved gemcitabine, cisplatin, and Y-90 microsphere radiation as a treatment option for bile duct cancer that cannot be removed with surgery.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Participants will be followed for up to 52 weeks if taken off protocol therapy.

It is expected that about 30 people will take part in this research study.

AstraZeneca, a pharmaceutical company, is supporting this research study by providing one of the study drugs, durvalumab, as well as providing research funding.

Sirtex, a medical device company, is supporting this research by providing the Y-90 radiation microsphere beads.

Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio

A Single Arm Phase 2 Study of Y-90 SIRT in Combination With Durvalumab (MEDI 4736) and Gemcitabine/Cisplatin in Locally Advanced, Unresectable or Metastatic Intrahepatic Cholangiocarcinoma

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

PFS is defined as the time from date of entry into the study until the date of disease progression (according to RECIST v1.1 and assessed by an independent central reviewer) or death, whichever occurs first.

All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms. Incidence is the number of patients experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.

OS is based on Kaplan-Meier method and defined as the time from date of entry into the study until the date of death.

ORR is defined as the proportion of participants with the best overall response of complete response or partial response according to RECIST v1.1 criteria as assessed by an independent central reviewer"

DCR is defined as the proportion of participants with the best overall response of complete response, partial response, or stable disease according to RECIST v1.1 criteria as assessed by an independent central reviewer

AstraZeneca

Sirtex Medical

Dana-Farber Cancer Institute

Beth Israel Deaconess Medical Center

Principal Investigator

TT-00420 (tinengotinib) tablets will be administered once daily in 21-day cycles with initial dosage of 10 mg QD.

TT-00420 (tinengotinib) tablet will be administered orally once daily per protocol defined schedule.

TT-00420 (tinengotinib)

Caixia Sun, PhD

Yueyin Pan, MD

Haitao Zhao, MD

Zengqing Guo, MD

Weimin Ding, MD

Zhenhui Lu, MD

Fei Yin, MD

Yanjiao Zhang, MD

Yanru Qin, MD

Xinfang Hou, MD

Feng Zhang, MD

Fuxiang Zhou, MD

Shanzhi Gu, MD

Yongchang Zhang, MD

Chuang Peng, MD

Weiwei Kong, MD

Ying Cheng, MD

Jingdong Zhang, MD

Meili Sun, MD

Zuoxing Niu, MD

Kui Wang, MD

Yusheng Wang, MD

Xielin Feng, MD

Lin Xie, MD

Jieer Ying, MD

Lin Shen, MD

Xu Zhu

Ming Yang, MD

Hao Chen, MD

Lan Zhang, MD

Tianqiang Song, MD

A phase II, open-label, multicenter study to evaluate the efficacy and safety of oral TT-00420 (Tinengotinib) tablets in subjects with cholangiocarcinoma who failed or relapsed to prior treatment of chemotherapy and FGFR Inhibitor.

Approximately 50 subjects will be enrolled. Eligible subjects will receive tinengotinib 10 mg QD orally as the initial dose level in 21-day cycles until confirmed disease progression, intolerable toxicity, death, or withdrawal of consent.

Study of TT-00420 (Tinengotinib) in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Chemotherapy and FGFR Inhibitor

A Phase II, Open-label, Multicenter Study to Evaluate the Efficacy and Safety of Oral TT-00420 (Tinengotinib) Tablets in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Prior Treatment of Chemotherapy and FGFR Inhibitor

The proportion of subjects who achieved a complete response (CR) or a partial response (PR) based on RECIST version 1.1.

From first study drug administration until the date of first documented progression or date of death from any cause, whichever came first

From first study drug administration until the date of death from any cause

The proportion of subjects who achieved a complete response (CR) or a partial response (PR) or a stable disease (SD) based on RECIST version 1.1.

Duration of response for CR or PR based on RECIST version 1.1.

As assessed per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 (or the most current version).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation	NCT06081829	Cholangiocarcin... Cholangiocarcin...	Ivosidenib	18 Years -	Servier
Nal-IRI and 5-FU Compared to 5-FU in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies	NCT03043547	Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin...	nal-IRI 5-FU leucovorin	18 Years -	AIO-Studien-gGmbH
Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio	NCT05655949	Bile Duct Cance... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Metastatic Intr...	Gemcitabine Cisplatin Durvalumab Yttrium-90	18 Years -	Beth Israel Deaconess Medical Center
Y-90 With Durvalumab/Gem/Cis in Intrahepatic Cholangio	NCT05655949	Bile Duct Cance... Cholangiocarcin... Cholangiocarcin... Cholangiocarcin... Metastatic Intr...	Gemcitabine Cisplatin Durvalumab Yttrium-90	18 Years -	Beth Israel Deaconess Medical Center
A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation	NCT06081829	Cholangiocarcin... Cholangiocarcin...	Ivosidenib	18 Years -	Servier
Study of TT-00420 (Tinengotinib) in Subjects With Cholangiocarcinoma Who Failed or Relapsed to Chemotherapy and FGFR Inhibitor	NCT06057571	Cholangiocarcin...	TT-00420 (tinen...	18 Years -	TransThera Sciences (Nanjing), Inc.

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