NCT05265208

Selective Internal Radiation Therapy and Capecitabine (Chemotherapy) Treatment for Liver Cancer

A Multicenter Open-label Randomized Controlled Prospective Phase II Study Evaluating the Efficacy of Selective Internal Radiation Therapy (Yttrium-90 Glass Microspheres) Combined With Capecitabine in the Neoadjuvant Setting of Operable Intrahepatic CHOlangiocarcinoma

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 62 (estimated)
• Sponsor: Center Eugene Marquis · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Treatment of intrahepatic cholangiocarcinoma (ICC) remains difficult. Many patients have unresectable tumors, and survival after resection was only slightly improved with the use of adjuvant capecitabine. One of the major prognostic factors is the resection margin, patients with invaded (R1) or narrow (\<5mm) margins having a higher risk of recurrence. Selective Internal Radiation Therapy (SIRT) with Yttrium-90 microspheres (also known as SIRT) is an interesting treatment in unresectable ICC. In a phase 2 study, the investigators showed a response rate of 39% and a disease control rate of 98%. Interestingly, 9 of the 41 patients were able to see their tumors downstages to surgery. It was also recently suggested in a retrospective study that patients resected after SIRT had a better prognosis than patients that could be operated upfront, despite less favorable initial tumor characteristics. Given the absence of validated neoadjuvant treatment, the promising activity of SIRT and chemotherapy combination in the unresectable setting, and the prognostic significance of close surgical margins, the aim of this trial is therefore to study this combination treatment in the neoadjuvant setting of resectable ICC.

Detailed description

The study plans to randomized eligible and consent patients in two balanced parallel groups, the one defined as the experimental arm while the second consisting in the actual standard of care is defined as the control standard arm. The experimental arm consists in 12 weeks of capecitabine combined with SIRT as neoadjuvant treatment followed by surgery. After SIRT, patients will be assessed at 10 weeks with thoracic-abdominal and pelvic CT scan and liver MRI. If the tumour is still deemed resectable, surgery will be performed at 16 weeks. In case of discovery of contra-indication to SIRT after inclusion (such as described in the SIRT exclusion criteria section) patients will stop chemotherapy and proceed to surgery within one month. The concerned patients are still included in the study and continue the post-surgery follow-up as expected by the protocol. In the control arm, patients will proceed to upfront surgery. The follow - up period begins just after the surgery in both arm, and the patients are evaluated every 3 months for 2 years, then every 6 months for 3 additional years, clinically by an oncologist and radiologically with thoracic-abdominal and pelvic CT scan. Whether progression occurred, patients will no longer be followed according to the protocol; only vital status continues to be collected until the end of the study (i.e. the last visit of the last patient).

Conditions

• Resectable Intrahepatic Cholangiocarcinoma

Interventions

Type	Name	Description
DRUG	Capecitabine	Capecitabine will given at 1250mg/m², 2 times a day with an interval of about 12 hours between two intakes, 2 weeks on, 1 week off, for 4 pre-surgery cycles.
DEVICE	Selective Internal Radiotherapy (SIRT)	During the first week of cycle 2 of capecitabine, patients will receive SIRT using Yttrium-90 glass microspheres. Treatment with Yttrium-90 glass microspheres requires two steps, one or two weeks apart. Both stages are performed under local anesthesia after a short hospitalization : the treatment simulation and therapeutic angiography.
PROCEDURE	Surgery	Surgery will be performed according to local practice.

Timeline

• Start date: 2022-02-04
• Primary completion: 2027-09-04
• Completion: 2030-02-04
• First posted: 2022-03-03
• Last updated: 2025-08-06

Locations

7 sites across 1 country: France