Combination treatment for advanced intrahepatic cholangiocarcinoma

A Phase III, Randomized, Three-arm, Double-blind, Placebo-controlled, International Multi-center Study to Evaluate the Efficacy and Safety of Toripalimab in Combination With Lenvatinib and Gemcitabine-based Chemotherapy Compared With Gemcitabine-based Chemotherapy as First-line Treatment in Patients With Unresectable Advanced Intrahepatic Cholangiocarcinoma (ICC)

This study is testing if a new combination of medications can help people with advanced liver cancer live longer and feel better compared to standard chemotherapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 480 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (Academic / other)
• Drugs / interventions: chemotherapy, toripalimab, lenvatinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05342194 on ClinicalTrials.gov

What this trial studies

This Phase III clinical trial evaluates the efficacy and safety of toripalimab combined with lenvatinib and gemcitabine-based chemotherapy as a first-line treatment for patients with unresectable advanced intrahepatic cholangiocarcinoma (ICC). Approximately 480 patients will be enrolled and randomly assigned to one of three treatment arms: the combination therapy, a placebo with chemotherapy, or a placebo with standard chemotherapy. The study aims to determine if the combination therapy improves outcomes compared to standard chemotherapy alone.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with unresectable advanced ICC who have not received prior systemic therapy.

Not a fit: Patients with resectable disease or those who have previously undergone systemic or targeted therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced ICC, potentially improving survival rates and quality of life.

How similar studies have performed: Other studies have shown promising results with similar combination therapies in advanced cancers, suggesting potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age of 18-75 years (inclusive), male or female;
2. Volunteer to participate in the study by signing the informed consent form and the ability to comply with the study protocol;
3. Advanced ICC with diagnosis confirmed by histology or cytology;
4. Stage II, III, or IV per TNM staging for ICC of the American Joint Committee on Cancer (AJCC) (8th edition, 2017). Those with Stage II or III should be determined to be unresectable by the investigator;
5. Patients with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization) for ICC. Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible;
6. Measurable lesion per RECIST v1.1;
7. Child-Pugh class A with no history of hepatic encephalopathy;
8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1;
9. Life expectancy ≥12 weeks;

Exclusion Criteria:

1. Diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC, sarcomatoid hepatocellular carcinoma, or hepatic fibrolamellar carcinoma by histology or cytology;
2. History of malignancy other than ICC within 5 years prior to screening, with the exception of localized malignancies that have been cured, including non-melanoma skin cancers, cervical carcinoma in situ, breast carcinoma in situ, and papillary thyroid carcinoma;
3. Prior radiotherapy for ICC within 4 weeks prior to randomization;
4. Major surgical procedures within 4 weeks prior to randomization;
5. Side effects from prior therapy (except alopecia and pigmentation) that has not recovered to ≤ grade 1 (per NCI-CTCAE v5.0) or levels specified in the inclusion/exclusion criteria;
6. Uncontrolled pericardial effusion, pleural effusion, or clinically significant moderate or severe ascites that is symptomatic or requires thoracentesis or paracentesis during the screening phase for control of symptoms;
7. Gastrointestinal (GI) hemorrhage within 6 months prior to randomization and/or gastrointestinal varices that have not been assessed and treated, if appropriate, within 6 months prior to randomization.
8. Gastrointestinal or non-gastrointestinal fistula, gastrointestinal perforation, or abdominal abscess within 6 months prior to randomization;
9. Ongoing or a history of recurrent intestinal obstruction. Patients with a single episode of intestinal obstruction that has fully resolved following treatment are eligible allowed;
10. History of serious cardiovascular and cerebrovascular diseases:
11. Significant bleeding and coagulopathy or other evidence of bleeding diathesis, to include:
12. Pre-existing CNS metastases and/or meningeal metastases (including dural metastases and leptomeningeal metastases);
13. Serious non-healing wound, active ulcer, or untreated bone fracture;
14. Vaccination with live virus or bacteria within 30 days prior to randomization;
15. Active autoimmune disease or history of autoimmune disease

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital affiliated to Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Jiazheng Yan

Conditions Intrahepatic Cholangiocarcinoma; Intrahepatic cholangiocarcinoma; Toripalimab; lenvatinib; Chemotherapy