First-line Treatment for Unresectable Locally Advanced Distal Cholangiocarcinoma Combining Radiotherapy and HAIC

NCT06370663 | Terminated Phase 2

• 1 other identifier: SDZLEC2023-109-01
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

The median survival of intrahepatic cholangiocarcinoma remains less than one year, highlighting the need for new treatments. Hepatic arterial infusion chemotherapy (HAIC), especially with fluoropyrimidine-based regimens, has shown promise in ICC treatment due to increased local drug concentration and reduced systemic toxicity. A combined approach of radiotherapy and HAIC with gemcitabine infusion may offer a hopeful strategy for locally advanced cholangiocarcinoma. However, clinical research on this combination is lacking as first-line therapy for unresectable ICC. Therefore, a single-center, single-arm study aims to assess this treatment approach's safety, efficacy, and molecular predictors. Improved HAIC delivery through modified percutaneous implantation provides a reliable pathway for effective treatment. In conclusion, exploring the synergistic effects of radiotherapy and HAIC in ICC could pave the way for more effective and personalized treatment strategies for this challenging cancer type.

Conditions

Intrahepatic Cholangiocarcinoma

Keywords

Intrahepatic Cholangiocarcinoma; Radiotherapy; Hepatic Arterial Infusion Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Assessing the severity of adverse events according to CTCAE v4.0.3 standards.

  2 year

Secondary Outcomes (1)

• Progression-Free Survival (PFS)

  2 year

Study Arms (1)

Radiotherapy plus HAIC

EXPERIMENTAL

Radiotherapy + Hepatic Arterial Infusion Chemotherapy (Gesitabine) + Chemotherapy (GEMOX)

Radiation: Radiotherapy; Drug: HAIC (GEMOX); Drug: Chemotherapy

Interventions

Radiotherapy RADIATION

Radiotherapy + Hepatic Arterial Infusion Chemotherapy (Gesitabine) + Chemotherapy (GEMOX)

Also known as: Hepatic Arterial Infusion Chemotherapy (GEMOX), Chemotherapy (Gesitabine)

Radiotherapy plus HAIC

HAIC (GEMOX) DRUG

Hepatic Arterial Infusion Chemotherapy (GEMOX)

Also known as: HAIC

Radiotherapy plus HAIC

Chemotherapy DRUG

Chemotherapy (Gesitabine)

Also known as: Chemotherapy (Gesitabine)

Radiotherapy plus HAIC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years, both male and female.
• Histologically or cytologically confirmed primary cholangiocarcinoma (including intrahepatic cholangiocarcinoma, hilar cholangiocarcinoma, and gallbladder carcinoma) or imaging-confirmed localized cholangiocarcinoma, staged as T1-4N0/N+M0 (according to AJCC 7th edition clinical staging).
• Ineligible for surgical treatment or refusal of surgical treatment upon pre-treatment assessment.
• Presence of measurable lesions as per RECIST v1.1 criteria for evaluation.
• ECOG performance status: 0-1.
• Expected survival of more than 6 months.
• Tolerable function of major organs for treatment.
• Non-surgically sterilized or premenopausal female patients need to use a medically accepted contraceptive method during the study treatment period and within 3 months after the end of the study treatment.

You may not qualify if:

• Subjects with any active autoimmune disease or a history of autoimmune disease are excluded.
• Patients with poorly controlled clinical symptoms or diseases related to the heart, such as:
• NYHA Class 2 or above heart failure
• Unstable angina
• Myocardial infarction within the past year
• Clinically significant ventricular or supraventricular arrhythmias requiring treatment or intervention
• QTc \>450 ms (males); QTc \>470 ms (females)
• Abnormal coagulation function (INR \>1.5 or PT \>16s), bleeding tendencies, or receiving thrombolytic or anticoagulant therapy.
• Subjects who have received radiation therapy, chemotherapy, steroid therapy, surgery, or molecular targeted therapy within less than 4 weeks (or 5 half-lives of the drug, whichever is longer) before the study drug's first dose, or who have not recovered from adverse events caused by previous treatment (excluding alopecia) to ≤Grade 1 according to CTCAE.
• Subjects with clinically symptomatic ascites, pleural effusion, or pericardial effusion requiring therapeutic puncture or drainage. Those who have had stable ascites or effusion after drainage of pleural or pericardial effusion for at least 2 weeks before the first dose of the study drug can be included in the study.
• Subjects with significant hemoptysis in the last 2 months or hemoptysis of half a teaspoon (2.5 ml) or more.
• Known hereditary or acquired bleeding and thrombotic tendencies (such as hemophiliacs, coagulation disorders, thrombocytopenia, splenomegaly, etc.) or those who have had arterial or venous thrombotic events within the last 6 months (prior to first SHR-1210 administration).
• Subjects with active infections or unexplained fever \>38.5°C during screening or before the first dose of the study drug.
• Patients with objective evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe lung function impairment, etc., either historically or currently.
• Subjects with congenital or acquired immunodeficiency (such as HIV infection) or active hepatitis (HBV reference: HBV DNA test value exceeds the upper limit of normal; HCV reference: HCV virus titer or RNA test value exceeds the upper limit of normal).

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Jinbo Yue

Jinan, Shandong, 250000, China

Location

Related Publications (8)

• Banales JM, Cardinale V, Carpino G, Marzioni M, Andersen JB, Invernizzi P, Lind GE, Folseraas T, Forbes SJ, Fouassier L, Geier A, Calvisi DF, Mertens JC, Trauner M, Benedetti A, Maroni L, Vaquero J, Macias RI, Raggi C, Perugorria MJ, Gaudio E, Boberg KM, Marin JJ, Alvaro D. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016 May;13(5):261-80. doi: 10.1038/nrgastro.2016.51. Epub 2016 Apr 20.

  PMID: 27095655 RESULT

• Valle J, Wasan H, Palmer DH, Cunningham D, Anthoney A, Maraveyas A, Madhusudan S, Iveson T, Hughes S, Pereira SP, Roughton M, Bridgewater J; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010 Apr 8;362(14):1273-81. doi: 10.1056/NEJMoa0908721.

  PMID: 20375404 RESULT

• Fiteni F, Nguyen T, Vernerey D, Paillard MJ, Kim S, Demarchi M, Fein F, Borg C, Bonnetain F, Pivot X. Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review. Cancer Med. 2014 Dec;3(6):1502-11. doi: 10.1002/cam4.299. Epub 2014 Aug 11.

  PMID: 25111859 RESULT

• Kim ST, Kang JH, Lee J, Lee HW, Oh SY, Jang JS, Lee MA, Sohn BS, Yoon SY, Choi HJ, Hong JH, Kim MJ, Kim S, Park YS, Park JO, Lim HY. Capecitabine plus oxaliplatin versus gemcitabine plus oxaliplatin as first-line therapy for advanced biliary tract cancers: a multicenter, open-label, randomized, phase III, noninferiority trial. Ann Oncol. 2019 May 1;30(5):788-795. doi: 10.1093/annonc/mdz058.

  PMID: 30785198 RESULT

• Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.

  PMID: 28596308 RESULT

• Zhang J, Wu L, Liu J, Lin M. A metastatic intrahepatic cholangiocarcinoma treated with programmed cell death 1 inhibitor: a case report and literature review. Immunotherapy. 2020 Jun;12(8):555-561. doi: 10.2217/imt-2019-0100. Epub 2020 May 6.

  PMID: 32372672 RESULT

• Jarnagin WR, Schwartz LH, Gultekin DH, Gonen M, Haviland D, Shia J, D'Angelica M, Fong Y, DeMatteo R, Tse A, Blumgart LH, Kemeny N. Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival. Ann Oncol. 2009 Sep;20(9):1589-1595. doi: 10.1093/annonc/mdp029. Epub 2009 Jun 2.

  PMID: 19491285 RESULT

• Konstantinidis IT, Groot Koerkamp B, Do RK, Gonen M, Fong Y, Allen PJ, D'Angelica MI, Kingham TP, DeMatteo RP, Klimstra DS, Kemeny NE, Jarnagin WR. Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone. Cancer. 2016 Mar 1;122(5):758-65. doi: 10.1002/cncr.29824. Epub 2015 Dec 22.

  PMID: 26695839 RESULT

MeSH Terms

Conditions

Cholangiocarcinoma

Interventions

Radiotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Jin Bo Yue, Dr.

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Radiation Oncology Department

Model Details: Combining radiotherapy with Hepatic Arterial Infusion Chemotherapy

Study Record Dates

• First Submitted: April 6, 2024
• First Posted: April 17, 2024
• Study Start: April 1, 2024
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)