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

Intrahepatic Cholangiocarcinoma Clinical Trial

Official title:

A Single-arm, Exploratory Phase II Clinical Trial of Combined Radiotherapy and HAIC as First-line Treatment for Unresectable Locally Advanced Distal Cholangiocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06370663
• Other study ID #: SDZLEC2023-109-01
• Status: Recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: April 1, 2026

Study information

• Verified date: April 2024
• Source: Shandong Cancer Hospital and Institute
• Contact: Jin Bo Yue, Dr.
• Phone: 0531-67626929
• Email: Len.Xu[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Intrahepatic cholangiocarcinoma (ICC) ranks as the second most common primary liver cancer, constituting 15%-20% of malignant liver tumors, with a rising incidence trend. Unlike hepatocellular carcinoma (HCC), ICC displays higher invasiveness and metastatic potential. Surgical resection remains the optimal treatment, yet many patients present with unresectable disease or metastasis, limiting surgical options. Chemotherapy, particularly the GC regimen, is standard for unresectable and metastatic ICC. Studies like ABC-02 have improved survival with GC chemotherapy compared to gemcitabine monotherapy. However, the median survival 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: April 1, 2026
• Est. primary completion date: April 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18-75 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.

Exclusion Criteria:

• 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:

1. NYHA Class 2 or above heart failure

2. Unstable angina

3. Myocardial infarction within the past year

4. Clinically significant ventricular or supraventricular arrhythmias requiring treatment or intervention

5. 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).

• Use of other investigational drugs within 4 weeks prior to the first dose of the study drug.

• Subjects with a history of or concurrent other malignancies (excluding cured basal cell carcinoma and cervical carcinoma in situ).

• Subjects who may receive other systemic anti-tumor therapies during the study.

• Subjects who have previously received PD-1 antibody therapy or immune therapy targeting PD-1/PD-L1.

• Vaccination with live vaccines within less than 4 weeks before the study drug's administration or potentially during the study period.

• Other factors judged by the investigator that may necessitate premature termination of the study.

Related Conditions & MeSH terms

• Cholangiocarcinoma
• Intrahepatic Cholangiocarcinoma

Intervention

Radiation:
• Radiotherapy
Radiotherapy + Hepatic Arterial Infusion Chemotherapy (Gesitabine) + Chemotherapy (GEMOX)

Drug:
• HAIC (GEMOX)
Hepatic Arterial Infusion Chemotherapy (GEMOX)
• Chemotherapy
Chemotherapy (Gesitabine)

Locations

Country	Name	City	State
China	Jinbo Yue	Jinan	Shandong

Sponsors (1)

Lead Sponsor	Collaborator
Shandong Cancer Hospital and Institute

Country where clinical trial is conducted

China, 

References & 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, — View Citation

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):1502-1 — View Citation

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 — View Citation

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 — View Citation

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 assoc — View Citation

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 S — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events	Assessing the severity of adverse events according to CTCAE v4.0.3 standards.	2 year
Secondary	Progression-Free Survival (PFS)	the length of time during and after treatment with a medication or therapy that a patient lives with the disease without it progressing	2 year