Nal-IRI and 5-FU Compared to 5-FU in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies

NCT03043547 | Completed Phase 2 DMC

• 2 other identifiers: AIO-HEP-01162016-003709-33
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

is an open label, randomized, multicenter phase II trial

Conditions

Cholangiocarcinoma Non-resectable; Cholangiocarcinoma Metastatic; Cholangiocarcinoma of the Gallbladder; Cholangiocarcinoma Advanced

Keywords

nal-IRI; 5-Fluorouracil

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  approx 42 months

Secondary Outcomes (4)

• Overall survival

  approx 42 months

• Objective tumor response rate (ORR) according to RECIST 1.1

  approx 42 months

• Toxicity/Safety

  approx 42 months

• Health related Quality of Life

  approx 42 months

Other Outcomes (4)

• biomarkers

  approx 42 months

• Immunohistochemistry of Carboxylesterase (CES)

  approx 42 months

• Analyse whole blood

  approx 42 months

Study Arms (2)

Nal-IRI + 5-FU + leucovorin (Arm A)

EXPERIMENTAL

nal-IRI \[Irinotecan liposome\] (80 mg/m2 as a 1.5 hour infusion), 5-FU \[5-Fluorouracil\] (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)

Drug: nal-IRI; Drug: 5-FU; Drug: leucovorin

5-FU + leucovorin (Arm B)

OTHER

Control intervention/standard arm: 5-FU (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)

Drug: 5-FU; Drug: leucovorin

Interventions

nal-IRI DRUG

nal-IRI \[Irinotecan liposome\] (80 mg/m2 as a 1.5 hour infusion)

Nal-IRI + 5-FU + leucovorin (Arm A)

5-FU DRUG

5-FU \[5-Fluorouracil\] (2400 mg/m2 as 46 hour infusion)

5-FU + leucovorin (Arm B); Nal-IRI + 5-FU + leucovorin (Arm A)

leucovorin DRUG

leucovorin (400 mg/m2 as 0.5 hour infusion)

5-FU + leucovorin (Arm B); Nal-IRI + 5-FU + leucovorin (Arm A)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent incl. participation in translational research and any locally-required authorization (EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry
• Histologically or cytologically confirmed, non-resectable, locally advanced or metastatic cholangiocarcinoma or gall bladder carcinoma
• Measurable or assessable disease according to RECIST 1.1
• Documented disease progression after prior gemcitabine or gemcitabine containing therapy, in locally advanced or metastatic setting. Examples of permitted therapies include, but are not limited to:
• Single agent gemcitabine
• Any one gemcitabine-based regimen, with or without maintenance gemcitabine
• ECOG performance status 0-1
• Adequate blood count, liver-enzymes, and renal function:
• ANC \> 1,500 cells/μL without the use of hematopoietic growth factors; and
• Platelet count ≥ 100 x 10\^9/L (\>100,000 per mm³) and
• Hemoglobin \> 9 g/dL (blood transfusions are permitted for patients with hemoglobin levels below 9 g/dL)
• Serum total bilirubin ≤ 3x upper normal limit (ULN) (biliary drainage is allowed for biliary obstruction; elevated bilirubin should be caused by obstruction not impaired liver function as assessed by albumin and INR values):
• Albumin levels ≥ 3.0 g/dL
• Patients not receiving therapeutic anticoagulation must have an INR \< 1.5 ULN and PTT \< 1.5 ULN within 7 days prior to randomization. The use of full dose anticoagulants is allowed as long as the INR or PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for anticoagulants for at least three weeks at the time of randomization

You may not qualify if:

• Active CNS metastases (indicated by clinical symptoms, cerebral oedema, steroid requirement, or progressive disease); patient should have been off steroids for at least 28 days prior to starting study therapy
• Clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion, or diarrhoea \> grade 1
• History of any second malignancy in the last 5 years; subjects with prior history of in-situ cancer or basal or squamous cell skin cancer are eligible. Subjects with other malignancies are eligible if they have been continuously disease free for at least 5 years.
• Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes or an unexplained fever \> 38.5°C during screening visits or on the first scheduled day of dosing (at the discretion of the investigator, patients with tumour fever may be enrolled), which in the investigator's opinion might compromise the patient's participation in the trial or affect the study outcome.
• Premalignant hematologic disorders, e.g. myelodysplastic syndrome
• Pre-existing lung disease
• Clinically significant cardiovascular disease in (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) 6 months before enrollment
• History of hypersensitivity to any of the study drugs or any excipient (nal-IRI, other liposomal products, fluoropyrimidines or leucovorin)
• Allogeneic transplantation requiring immunosuppressive therapy or other major immunosuppressive therapy
• Severe non-healing wounds, ulcers or bone fractions
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedures, except open biopsy, nor significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgical procedure during the course of the study except for surgery of central intravenous line placement for chemotherapy administration.
• Medication that is known to interfere with any of the agents applied in the trial.
• Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). \[Acceptable methods of contraception are:implants, injectable contraceptives, combined oral contraceptives, intrauterine pessaries (only hormonal devices), sexual abstinence or vasectomy of the partner\].
• Known Gilbert-Meulengracht syndrome

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Servier: collaborator

Study Sites (1)

Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Related Publications (2)

• Yoo C, Saborowski A, Hyung J, Wenzel P, Kim I, Wege H, Kim KP, Folprecht G, Ryoo BY, Schutt P, Cheon J, Gotze T, Ryu H, Lee JS, Vogel A. Liposomal irinotecan for previously treated patients with biliary tract cancer: A pooled analysis of NIFTY and NALIRICC trials. J Hepatol. 2025 Oct;83(4):909-916. doi: 10.1016/j.jhep.2025.03.013. Epub 2025 Mar 25.

  PMID: 40147791 DERIVED

• Vogel A, Saborowski A, Wenzel P, Wege H, Folprecht G, Kretzschmar A, Schutt P, Jacobasch L, Ziegenhagen N, Boeck S, Zhang D, Kanzler S, Belle S, Mohm J, Gokkurt E, Lerchenmuller C, Graeven U, Pink D, Gotze T, Kirstein MM. Nanoliposomal irinotecan and fluorouracil plus leucovorin versus fluorouracil plus leucovorin in patients with cholangiocarcinoma and gallbladder carcinoma previously treated with gemcitabine-based therapies (AIO NALIRICC): a multicentre, open-label, randomised, phase 2 trial. Lancet Gastroenterol Hepatol. 2024 Aug;9(8):734-744. doi: 10.1016/S2468-1253(24)00119-5. Epub 2024 Jun 10.

  PMID: 38870977 DERIVED

Related Links

• AIO - Working Group for Medical Oncology from the German Cancer Society
• AIO-Studien-gGmbH

MeSH Terms

Interventions

irinotecan sucrosofate; Fluorouracil; Leucovorin

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Arndt Vogel, Prof.

  Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2017
• First Posted: February 6, 2017
• Study Start: October 24, 2017
• Primary Completion: December 8, 2021
• Study Completion: March 8, 2022
• Last Updated: May 18, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)