PEHRICCA : PErioperative CISGEM plus RILVEGOSTOMIG in High-Risk resectable Intrahepatic CholangioCarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 May 2026 → ongoing

Decision date (initial)

2025-10-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

Progression-free survival at 12 months

Secondary objectives 10

1. R0/R1 Resection rate
2. Best overall response
3. Overall survival, median OS, 12 and 24 month-OS
4. Progression Free Survival: median PFS, 24 month-PFS
5. Disease Free Survival in resected patients: median DFS, 12 and 24 month-DFS
6. Dropout rate before surgery
7. Complete treatment rate (Pre-op and post-op)
8. Pathological response (resected patients)
9. Safety: treatment-related AEs, immune related AEs, post-operative complications (Clavien Dindo)
10. Quality of life (QLQ-C30 +BIL21) questionnaires

Conditions and MedDRA coding

Hihg risk of cholangiocarcinoma intra hépatic resectable

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Age ≥ 18 years
2. WHO PS 0-1
3. Body weight > 30kg
4. Histo/cytologically proven intrahepatic cholangiocarcinoma
5. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors RECIST 1.1 criteria ».
6. Naive to systemic treatment and loco regional treatment for biliary tract cancer
7. Resectable disease with at least one of the following high-risk criteria of post resection relapse: • Tumor Size ≥ 50 mm and/or tumor number > ou = 3 nodules (maximum 5, in the same lobe), satellite nodules may be included ((intrahepatic metastases <2 cm at <2 cm from the primary nodule) • cN1 (according to TNM classification 8th edition 2017): hilar, peri duodenal and peri pancreatic adenopathy for iCCA of right liver and hilar, inferior phrenic, gastrohepatic, adenopathy for iCCA of left liver • Risk of R1 margin: distance < 10 mm from major structures, i.e., the right and left glissonian pedicles and/or hepatic veins (to be discussed during a MDT) • Macrovascular invasion (portal vein and/or sus hepatic veins and/or vena cava invasion). • ❖ (Liver MRI with PRIMOVIST contrast injection if possible, and diffusion-weighted sequences)
8. Adequate organ function, as defined by the following: • Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 2,5 x Upper Limit of Normal (ULN) • Total serum bilirubin ≤1.5 ULN This will not apply to patients with confirmed Gilbert’s syndrome • Prothrombin ratio > 70% and/or Factor V> 70% in case of oral anticoagulation therapy • Serum albumin ≥ 30 g/L • Haemoglobin ≥ 10 g/dl and no transfusion within 4 weeks before inclusion • Absolute Neutrophil Count (ANC) ≥ 1,500/μL • Platelets ≥ 150,000/μL
9. Creatinine clearance ≥45 ml/min (calculated by CKD-EPI)
10. Life expectancy ≥ 3 months
11. Female Patients postmenopausal for at least one year or surgically infertile for at least 6 weeks, or highly effective contraception for male and female patients of childbearing potential for the duration of study and for 7 months after the last dose of drug for female and 4 months for male.
12. A negative pregnancy test for inclusion for all female patients of child-bearing potential
13. Patient covered by a plan of the French Social Security system
14. Written informed consent obtained from the patient prior to performing any protocol-related procedures
15. Patient with available tumor tissue sample for the study or willing to have a biopsy

Exclusion criteria 17

1. Existence of metastases or distant lymph node involvement considered as metastatic
2. Locally advanced disease considered as definitively non resectable
3. Cirrhosis with Child ≥ B7 a. Any history of liver decompensation: hepatic encephalopathy, presence of ascites b. Presence of clinically significant portal hypertension (platelets counts < 150G/L and/or liver stiffness > 20kPa and/or presence of oesophageal and/or gastric varices)
4. Mixed histology (hepatocholangiocarcinoma)
5. Persistent toxicities (>CTCAE grade 2) caused by previous cancer therapy, excluding alopecia.
6. Contraindication to immunotherapy: Active or prior documented autoimmune or inflammatory disorders or any severe or uncontrolled systemic disease
7. Current or prior use of immunosuppressive medication within 14 days before the first dose
8. History of allogenic organ transplantation
9. Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients (cisplatin, gemcitabine and Rilvegostomig)
10. Live vaccine administration within 30 days prior to the first dose of study treatment Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 6 months after the last dose of investigational product
11. Uncontrolled infection with human immunodeficiency virus (HIV). Required conditions for inclusion are as follows: undetectable viral RNA, CD4+ count ≥350 cells/μL, no history of AIDS-defining opportunistic infection within the past 12 months, stable condition for at least 4 weeks on the same anti-HIV medications.
12. Active and untreated infection with hepatitis B and/or hepatitis C Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen [HBc] antibody test) are eligible.
13. Other active cancer or history of cancer within 2 years, except for carcinoma in situ of the cervix or basal cell or squamous cell skin carcinoma or any other carcinoma in situ, considered cured
14. History of clinically significant arrhythmia, cardiomyopathy of any etiology; symptomatic congestive heart failure (as defined by New York Heart Association class ≥ 3), history of myocardial infarction within the past 6 months. Participation in another clinical study with an investigational product during the last 4 weeks
15. Pregnant or breastfeeding woman
16. Persons deprived of liberty or under guardianship or incapable of giving consent
17. Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint of the study is the Progression-Free survival at 12 months. Events to consider for the evaluation of the endpoint are: - Progression (local or metastatic) during the pre-operative chemotherapy - Progression (local or metastatic) during post-operative chemotherapy - Death (all cause)

Secondary endpoints 9

1. Resection rate: This rate is defined as the proportion of patients who could benefit from surgery after the pre-operative chemotherapy. Types of resections will also be collected (R0/R1/R2)
2. Dropout rate before surgery: This rate is defined as the proportion of patients who could not benefit from surgery after pre-operative chemotherapy
3. Overall survival (OS): OS is defined by the time between the date of inclusion and the date of death (regardless of the cause). Alive patients will be censored at the date of their last news
4. Best Response: The response is defined regarding RECIST 1.1 criteria evaluated using pre-operative imageries during treatment. Best response will be classified as: - Objective Response: patients with partial or complete response. - Stability - Progression
5. Disease-Free survival (DFS): DFS is defined by the time between the date of surgery and the date of first local or metastatic progression or death (regardless of the cause) Alive patients without progression will be censored at the date of their last news
6. Pathological response (resected patients): This endpoint will be evaluated according to the TRG (Rubbia-Brandt L et al. Annals Oncol 2007) 20. This response is evaluated according to the various categories: TRG1/TRG 2/TRG 3/TRG 4/TRG 5
7. Adverse events: Adverse events will be evaluated according to NCI-CTC v5.0.and complications post operation according to Clavien-Dindo classification
8. Percentage of pre-operative and post-operative completion (4 cycles planned) is defined as the percentage of patients who received the 4 cycles of chemotherapy even if doses are partially or not delivered for a product. The percentage will be calculated separately for pre and post-operative periods
9. Quality of life: The QLQ-C30 is a cancer-specific tool composed of 30 items. Five functional scores (physical, role, cognitive, social, and emotional), a global health score ranging from 0 (worst) to 100 (best) have been developed as well as 9 symptom scores (nausea, pain, fatigue, dyspnea, difficulty sleeping, anorexia, constipation, diarrhea and perceived financial difficulties) ranging from 0 (best) to 100 (worse).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon

Postcode

21000

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

GAEL ROTH

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

GAEL ROTH

Third parties 1

Locations

1 EU/EEA country · 31 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications