Neoplasms

All Conditions

Rare Diseases

Cholangiocarcinoma

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Lenvatinib

Protein Kinase Inhibitors

Enzyme Inhibitors

Cryoablation treatment starts at day 0. Sintilimab and Lenvatinib will be initiated on day 1 after cryoablation. Sintilimab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.

Cryoablation is performed under US or CT guidance per Investigator decision.

Cryoablation

Sintilimab

Peng Wang, MD

Peng Wang, M.D.

The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.

Recent studies have suggested that local destruction of tumor tissue by cryoablation induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed increased ORR in many types of human cancers. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.

Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)

A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined With Sintilimab Plus Lenvatinib as First-line Treatment in Patients With Unresectable Advanced Intrahepatic Cholangiocarcinoma (ICC)

ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.

DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.

PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)

OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death

DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.

Fudan University

Clinical Professor

Cohort_1:HMPL-453 150mg QD continuously in 21-day cycles; Cohort_2:HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Day 1 to 14\], followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle)

HMPL-453

Bo Zhang

Jessica Zhang

Jianming Xu

Jianming Xu, PhD

Weiguo Su, PhD

The goal of this clinical trial is to evaluate in patients with advanced intrahepatic cholangiocarcinoma harboring FGFR2 fusion/rearrangement. The main questions it aims to answer are:

• To evaluate the objective response rate (ORR) of HMPL-453 tartrate in the treatment of patients with advanced intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor (FGFR) 2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance Participants will receive HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Days 1 to 14\] followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle.\]

This is an open-label, single-arm, multicenter phase 2 clinical study to evaluate the efficacy and safety of HMPL-453 tartrate in the treatment of patients with advanced ICC harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance. The study consists of cohort 1 and cohort 2.

Cohort 1: Approximately 12 patients with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are planned to be enrolled in this cohort to receive HMPL-453 tartrate 150 mg administered orally once daily (QD) continuously in 21-day cycles.

Cohort 2: A total of approximately 113-116 patients are planned to be enrolled in this cohort, divided into safety run-in and extension phases. Approximately 6 to 9 patients with solid tumors who failed standard treatment or had intolerable toxicity will be enrolled into the first phase (safety run-in phase), to receive HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Day 1 to 14\], followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle). Dose limiting toxicities (DLT) observation period consists of 28 days, in which a cycle of treatment will be received. Patients will enter second stage of cohort 2 (extension phase) after completion of safety run-in assessments. Approximately 20 patients with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance will receive HMPL-453 tartrate 300 mg QD orally administered (for 14 consecutive days \[Day 1 to 14\], followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle). Based on the efficacy and safety data of the already enrolled patients, and after reaching an agreement with China Center for Drug Evaluation, approximately 90 additional patients with locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 fusions/rearrangements after at least one line of systemic treatment failure or intolerance are being enrolled to support registration submission as the registration study stage of this study, receiving HMPL-453 tartrate 300 mg QD orally (for 14 consecutive days \[Days 1 to 14\] followed by 7 days off \[Day 15 to 21\], 21 days as a treatment cycle.

Phase 2 Study of HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma

An Open-Label, Single-Arm, Multicenter Phase 2 Clinical Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-453 Tartrate in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusion/Rearrangement

Proportion of patients whose best overall response are confirmed CR or PR

Proportion of patients whose best overall response after treatment is confirmed CR or PR, or judged as SD (SD≥6 weeks)

The time from the first dose of study drug to the first CR or PR in patients whose best overall response is a confirmed CR or PR

The time from initial CR or PR to PD or death from any cause, whichever comes first, in patients whose best overall response is a confirmed CR or PR

The time from the first study treatment to the onset of PD or death from any cause

The time from the patients receiving the first study drug until the death due to any cause

Hutchmed

Micronutrients

Bone Density Conservation Agents

Vasoconstrictor Agents

Vitamins

Leucovorin

Fluorouracil

Vitamin D

Cholecalciferol

Mitomycins

Mitomycin

Calcitriol

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

12 mcg Calcitriol will be given orally three times per week for 6 months. In this portion of the study, all patients will get the same dose of calcitriol along with the standard chemotherapy (5-fluorouracil-mitomycin C-leucovorin).

Vajarabhongsa Bhudisawasdi, MD

Sopit Wongkham, PhD

Cholangiocarcinoma (CCA), cancer of the bile duct, is the first cause of cancer death of the people in the northeast of Thailand. The incidence of CCA in this region is highest not only in the country but in the world. CCA is a slow growing but highly metastatic tumor. At present, there is no standard chemotherapy or effective treatment for CCA. Most of the patients have short survival after diagnosis. Strong evidences from in vitro, animal and clinical studies indicate that vitamin D can prevent and control growth of cancer. Our preclinical studies in CCA cell lines, animal and patient tissue culture indicate that vitamin D effectively reduce growth of CCA. Supplementation of vitamin D to chemotherapeutic drugs enhance drug toxicity and better response. At present, there are several clinical trials in USA on supplementation of vitamin D or its analogs to cancer patients. The side effect or toxicity of using vitamin D supplementation is low, some patients had stable disease and some had good response. The current study is set up a clinical trial phase II of vitamin D (calcitriol) in combination with 5-fluorouracil, Mitomycin C and Leucovorin in an open label-non-randomized study to evaluate the tumor response in patients with advanced intrahepatic cholangiocarcinoma. This study will provide an alternative/effective chemotherapy treatment for CCA patients. Better survival and improved quality of life are also expected.

* OUTLINE: This is a dose-limiting toxicity study of calcitriol.
* EVALUAITON: During the initial phase, 14 patients will be accrued for this study. If the number of patient's response to calcitriol and 5-fluorouracil/mitomycin C/leucovorin is less than 1/14, the study will be stopped. However there is one patient who responses to calcitriol and 5-fluorouracil/mitomycin C/leucovorin, the new 14 patients will be accrued during the secondary phase of study.

Calcitriol in Advanced Intrahepatic Cholangiocarcinoma

A Clinical Trial Phase II of Calcitriol in Combination With 5-fluorouracil, Mitomycin C and Leucovorin in an Open Label-non-randomized Study to Evaluate the Tumor Response in Patients With Advanced Intrahepatic Cholangiocarcinoma

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)	NCT05835245	Advanced Intrah...	Cryoablation Sintilimab Lenvatinib	18 Years -	Fudan University
Phase 2 Study of HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma	NCT04353375	Advanced Intrah...	HMPL-453	18 Years -	Hutchmed
Phase 2 Study of HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma	NCT04353375	Advanced Intrah...	HMPL-453	18 Years -	Hutchmed
Calcitriol in Advanced Intrahepatic Cholangiocarcinoma	NCT01039181	Advanced Intrah...	Calcitriol	30 Years - 65 Years	National Science and Technology Development Agency, Thailand
Calcitriol in Advanced Intrahepatic Cholangiocarcinoma	NCT01039181	Advanced Intrah...	Calcitriol	30 Years - 65 Years	National Science and Technology Development Agency, Thailand
Phase 2 Study of HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma	NCT04353375	Advanced Intrah...	HMPL-453	18 Years -	Hutchmed

Spots Global Cancer Trial Database for advanced intrahepatic cholangiocarcinoma