Neoplasms

All Conditions

Digestive System Diseases

Rare Diseases

Cholangiocarcinoma

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Biliary Tract Diseases

Gastrointestinal Diseases

Bile Duct Cancer

Biliary Tract Cancer

Gallbladder Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Pembrolizumab

Cisplatin

Durvalumab

Antimetabolites

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Zanidatamab plus standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.

Standard of care treatment of CisGem with or without a PD-1/L1 inhibitor. PD-1/L1 inhibitor will be physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations.

Zanidatamab

Clinical Trial Disclosure & Transparency

The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a programmed death protein 1/ligand-1 (PD-1/L1) inhibitor (physician's choice of either Durvalumab or Pembrolizumab, where approved under local regulations) as first line of treatment for participants with human epidermal growth factor receptor 2 (HER2)-positive biliary tract cancer.

Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer

An Open-label Randomized Trial of the Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy Alone for Advanced HER2-positive Biliary Tract Cancer

PFS is defined as the time from the date of randomization to the date of documented disease progression, or death from any cause.

OS is defined as the time from randomization to death, due to any cause.

Confirmed objective response rate is defined as achieving a confirmed best overall response of Complete Response (CR) or Partial Response (PR)

Duration of response is defined as the time from the first objective response (CR or PR) to documented Progressive Disease (PD) or death, from any cause.

TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30) final scores range from 0 to 100, where higher scores reflect better functioning

TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC QLQ-C30 final scores range from 0 to 100, where higher scores reflect better functioning.

TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer module (QLQ-BIL21) (Pain, Jaundice, Abdominal Pain, and Pruritis) final scores range from 0 to 100, where higher scores reflect better functioning.

TDD is defined as the time from randomization to the first confirmed clinical meaningful deterioration or death. EORTC QLQ-BIL21 (Pain, Jaundice, Abdominal Pain, and Pruritis) final scores range from 0 to 100, where higher scores reflect better functioning.

Jazz Pharmaceuticals

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

ICP-192 is a round, uncoated tablet, 5mg, orally.

ICP-192

Jin Li

Lianxin Liu

Xiao Li

Haitao Zhao

Chunwang Yuan

Hongyong Zhang

Xu Zhu

Yunbo Zhao

Hailan Lin

Yanling Chen

Kecan Lin

Jing Wu

Chao Liu

Ruihua Xu

Weiming Ding

Fei Yin

Zhiwei Li

Xinfang Hou

Qingxia Fan

Fuxiang Zhou

Zhang Feng

Chuang Peng

Shanzhi Gu

Feizhou Huang

Bi Yanzhi

Lichun Deng

Shen Jie

Zhixiang Zhuang

Jinsong Li

Jianbing Wu

Chaoliu Dai

Jingdong Zhang

Qiang Tu

Ping Chen

Jikai Yin

Yufeng Cheng

MeiLi Sun

ZuoXing Niu

Tian He

Zhou Jian

Kui Wang

Xielin Feng

Lunan Yan

Wei Lu

Jieer Ying

Wu zhang

Tingbo Liang

This is a single-arm, open-label, multi-center phase 2 clinical trial of ICP-192. The purpose of this study is to evaluate the efficacy and safety in patients with FGFR2-Rearranged unresectable or metastatic intrahepatic cholangiocarcinoma who failed prior therapy

A Study of ICP-192 in Patients With FGFR2-Rearranged Unresectable or Metastatic Intrahepatic Cholangiocarcinoma

A Single-Arm, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of ICP-192 in Subjects With Unresectable or Metastatic Intrahepatic Cholangiocarcinoma With FGFR2 Fusions/Rearrangements Who Have Failed Prior Therapy

Beijing InnoCare Pharma Tech Co., Ltd.

Immunomodulating Agents

Radioembolization with Y-90 will be performed in nominal day 0

radioembolization with Y-90

Following radioembolization, for 6 cycles -intravenous infusion on day 1 of each cycle

Following radioembolization, for 6 cycles -intravenous infusion on day 1 and 8 of each cycle

Francesco De Cobelli, MD

Stephanie Steidler, PhD

Francesca Ratti, MD

Underlying disease mechanisms are fundamental for correct treatment selection and patient management in highly invasive and debilitating non-transmissible diseases. Even though overall disease burden of cancer may have decreased due to a higher degree of awareness, the availability of high-quality healthcare and early diagnosis may become challenging in certain neoplasms. Cholangiocarcinoma is usually diagnosed at advanced stages due to non-specific presentation and is frequently refractory to chemotherapy, causing a massive impact on patients and their families. Surgery is currently the only curative treatment but is available to only approximately 30% of patients. The combination of interventional- and immune-oncology to standard of care creates the perfect substrate for synergistic mechanisms to fight tumor growth; in situ cell death following transarterial embolization(TARE) elicits immune mediated response, inflammatory response and biomarkers of oxidative stress and increases antigen presenting T-cells which an anti-anti progam death ligand (PD-L)1 can bind to; standard of care can then add on with its known effects.The rationale of a combined- locoregional and systemic - treatment lies in the synergistic effects of each of the treatments.

Tumors are highly selective and well defined abnormal cellular proliferations in which microenvironment plays an important role in response to treatment. Intrahepatic Cholangiocarcinoma (iCCA), a tumor derived from the epithelia cells of the bile duct, is particularly invasive and malignant. Personalized treatment options with documented efficacy in patients with iCCA are still not available due to the complex and heterogenous molecular pathogenesis which has not been holistically described. Disease models have limited reproducibility; underlying chronic cholestatic disease, chronic inflammation and risk factors contribute to the complexity and diversity of tumor microenvironment. Although novel systemic therapeutic agents show improvement compared to standard of care chemotherapy, a significant percentage of patients still does not respond to treatment, maybe due to molecular/immunologic features which confer resistance. Local treatment prior to systemic therapy has shown to induce subtle changes in the tumor microenvironment and a systemic immune response: engagement of the immune system may therefore lead to enhanced and long term immunosurveillance and therefore, lasting benefits for cancer patients.

Combined systemic treatment with an anti PD-L1, that binds to the programmed cell death protein 1, and the standard of care (SOC) protein kinase inhibitor sorafenib and gemcitabine (which inhibits DNA synthesis), have been used in clinical trials for other primary liver indications and in patients with biliary tract cancers (TOPAZ trial).

Radioembolization (TARE) combines the embolization properties of microspheres with the radiant effect of Yttrium-90 (Y-90). The locally treated tumor tissue is left in place and releases tumor-associated antigens and danger-associated molecular peptides originating from dead or dying cancer cells which promote the activation of antigen presenting cells and anti-tumor CD8+T cells. The resulting development of a systemic immune response following local treatment may lead to tumor regression at different sites than the one treated locally, leading to the so-called abscopal effect.

Comprehensive evaluations in patients undergoing combined treatment may allow a better understanding of tumor pathophysiology as well as the optimization of combined treatment schemes.

This study will investigate the efficacy, primary endpoint overall response rate according to mRECIST (modified Response Evaluation Criteria in Solid Tumors) , and safety of the association of locoregional radioembolization followed by the combination of standard of care (SOC) chemotherapy with Cisplatin and Gemcitabine and durvalumab in patients with liver predominant unresectable intrahepatic cholangiocarcinoma. The biological profile of patients prior to and following locoregional treatment and the effect of systemic therapy will be characterized in terms of potential biomarkers such as quantitative non-invasive radiological based parameters, tumor tissue profiling and evaluation of biological substrates to help define and stratify patients with higher response and better outcome.

Precision Medicine in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization and Combined Biological Therapy

Single Arm, Multicenter Phase II Study Investigating the Efficacy and Safety of a Novel Therapeutic Scheme in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization in Combination With CisGem and Durvalumab (MEDI4736)

mRECIST criteria on imaging (modified Response Evaluation Criteria in Solid Tumors criteria)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer	NCT06282575	Biliary Tract C... HER2 Gene Mutat...	Zanidatamab Cisplatin Gemcitabine Pembrolizumab Durvalumab	18 Years -	Jazz Pharmaceuticals
A Study of ICP-192 in Patients With FGFR2-Rearranged Unresectable or Metastatic Intrahepatic Cholangiocarcinoma	NCT05678270	Intrahepatic Ch...	ICP-192	18 Years -	Beijing InnoCare Pharma Tech Co., Ltd.
Precision Medicine in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization and Combined Biological Therapy	NCT06375915	Intrahepatic Ch...	radioembolizati... Durvalumab Cisplatin Gemcitabine	18 Years - 80 Years	IRCCS San Raffaele
Precision Medicine in Patients With Unresectable CholAngiocarcinoma: RadioEmbolization and Combined Biological Therapy	NCT06375915	Intrahepatic Ch...	radioembolizati... Durvalumab Cisplatin Gemcitabine	18 Years - 80 Years	IRCCS San Raffaele
A Study of ICP-192 in Patients With FGFR2-Rearranged Unresectable or Metastatic Intrahepatic Cholangiocarcinoma	NCT05678270	Intrahepatic Ch...	ICP-192	18 Years -	Beijing InnoCare Pharma Tech Co., Ltd.
A Study of ICP-192 in Patients With FGFR2-Rearranged Unresectable or Metastatic Intrahepatic Cholangiocarcinoma	NCT05678270	Intrahepatic Ch...	ICP-192	18 Years -	Beijing InnoCare Pharma Tech Co., Ltd.
Efficacy and Safety of Zanidatamab With Standard-of-care Therapy Against Standard-of-care Therapy for Advanced HER2-positive Biliary Tract Cancer	NCT06282575	Biliary Tract C... HER2 Gene Mutat...	Zanidatamab Cisplatin Gemcitabine Pembrolizumab Durvalumab	18 Years -	Jazz Pharmaceuticals

Spots Global Cancer Trial Database for intrahepatic cholangiocarcinoma (icc)