Yttrium‑90 internal radiation plus capecitabine before liver surgery for intrahepatic cholangiocarcinoma

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

This project will try giving Y‑90 internal radiation together with capecitabine before surgery to shrink resectable intrahepatic cholangiocarcinoma and reduce the risk of close surgical margins.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 62 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Center Eugene Marquis (Academic / other)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 7 sites (Rennes, Brittany Region and 6 other locations)
• Trial ID: NCT05265208 on ClinicalTrials.gov

What this trial studies

This is a randomized phase 2 trial comparing neoadjuvant selective internal radiation therapy (SIRT) with Yttrium‑90 plus 12 weeks of capecitabine versus immediate (upfront) surgery for patients with resectable intrahepatic cholangiocarcinoma at high risk of narrow margins. Patients in the experimental arm receive SIRT and oral capecitabine, undergo imaging at about 10 weeks, and—if still resectable—proceed to surgery around week 16; patients in the control arm go directly to surgery. After surgery all patients enter the same follow‑up schedule with clinical reviews every 3 months for 2 years and then every 6 months for 3 more years, with CT imaging at the scheduled visits. Key eligibility includes age >18, ECOG <2, histologically proven ICC judged resectable but with predicted close margins, and adequate organ function, while advanced fibrosis/cirrhosis or major lab abnormalities exclude participation.

Who should consider this trial

Good fit: Adults with histologically confirmed intrahepatic cholangiocarcinoma judged technically resectable but at significant risk of close margins, ECOG performance status 0–1, no prior ICC treatment, and adequate blood, liver, and kidney function are ideal candidates.

Not a fit: Patients with advanced fibrosis or cirrhosis (F3–F4), significant abnormal labs, contraindications to SIRT (for example unsafe lung shunt or non‑target embolization risk), unresectable disease, or prior treatment for ICC are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase the number of patients who have wider surgical margins or who can be safely downstaged to surgery, potentially improving long‑term outcomes.

How similar studies have performed: Prior phase 2 work of SIRT in unresectable ICC reported a 39% response rate, 98% disease control, and some patients downstaged to surgery, but neoadjuvant use before planned resection remains not yet validated.

Eligibility criteria

Inclusion Criteria:

1. Age \> 18 years-old,
2. ECOG Performance Status \<2,
3. Histologically-proven ICC,
4. No previous treatment for ICC,
5. Tumour deemed resectable by a hepatobiliary surgeon, validated by a Surgical Review Board,
6. Significant risk of close margins, defined as:

   1. Resection margin predicted by the surgeon \<1 cm
   2. Tumour \>5 cm
   3. Multifocal lesion deemed resectable, validated by a Surgical Review Board
7. Registration with a social security scheme,
8. Patient information and signature of informed consent or legal representative.

Non-inclusion Criteria:

1. Severe fibrosis (F3) ou cirrhosis (F4),
2. Inadequate haematological, hepatic, renal and coagulation functions:

   1. Haemoglobin ≤ 8,5 g/dl
   2. Neutrophils \< 1,5 Giga/L
   3. Platelets \< 60 Giga/L
   4. Bilirubin \> 34 µmol/L
   5. ASAT/ALAT \> 5 x ULN
   6. Creatinine clearance \< 30 ml/min (MDRD)
   7. TP et INR \> 2,3 ULN
   8. TCA \> 1,5 x ULN
3. Uracil blood level \>16 ng/mL,
4. Respiratory insufficiency,
5. Comorbidity precluding surgical resection, such as severe heart disease,
6. Presence of microvacuolar steatosis \> 60% or regenerative nodular hyperplasia, for patients for whom a major hepatectomy is planned,
7. Contraindication to hepatic artery catheterization (vascular abnormalities, bleeding diathesis),
8. Previous chemotherapy (including for another cancer),
9. Previous abdominal (supra-mesocolic) radiotherapy (including for another cancer),
10. Other invasive malignancies,
11. Patient participate to an interventional study that tests another medical intervention before surgery,
12. Pregnant woman or likely to be or breastfeeding, or male or female patients of reproductive potential without effective contraception from screening to 30 days after the end of the treatment adjuvant,
13. Minors, individual deprived of liberty, or under any kind of guardianship,
14. Patients unable to submit to medical follow-up of the study for social, medical or psychological reasons.

Exclusion Criteria:

1. Pulmonary shunt with dose \>30Gy,
2. Digestive shunting, non-correctible by interventional radiology,
3. Absence of fixation of MAA in the tumour.

Where this trial is running

Rennes, Brittany Region and 6 other locations

• Centre de Lutte contre le Cancer Eugène Marquis — Rennes, Brittany Region, France (Recruiting)
• Groupe SUD-Haut-Lévêque - Centre Hospitalier Universitaire de Bordeaux — Pessac, New Aquitaine, France (Recruiting)
• Centre Hospitalier Universitaire de Montpellier — Montpellier, France (Active_not_recruiting)
• Centre Hospitalier Universitaire de Poitiers — Poitiers, France (Active_not_recruiting)
• Gustave Roussy — Villejuif, France (Recruiting)
• Hôpital Beaujon — Clichy, Île-de-France Region, France (Recruiting)
• Hôpital Henri - Mondor — Créteil, Île-de-France Region, France (Active_not_recruiting)

Study contacts

• Principal investigator: Julien Edeline, MD — Centre de Lutte contre le Cancer Eugène Marquis
• Study coordinator: Marion Trochet

Conditions Resectable Intrahepatic Cholangiocarcinoma; Selective Internal Radiation Therapy