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Cholangiocarcinoma Non-resectablePhase 2NALIRICCNCT03043547

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

A Phase 2 study testing nal-IRI, 5-FU and leucovorin in people with Cholangiocarcinoma Non-resectable and Cholangiocarcinoma Metastatic, run by AIO-Studien-gGmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

is an open label, randomized, multicenter phase II trial Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
nal-IRI, 5-FU and leucovorin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
1 siteGermany
Study dates
24 Oct 2017to 8 Mar 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • AST (SGOT)/ALT (SGPT) ≤ 5 x institutional upper limit of normal
  • Serum Creatinine ≤ 1.5 x ULN and a calculated glomerular filtration rate ≥ 30 mL per minute
  • Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of treatment.
  • Subject is willing and able to comply with the protocol (including contraceptive measures) for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • 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
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  • 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
  • Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
  • Participation in another clinical study with an investigational product during the last 30 days before inclusion or 5 half-lifes of previously used trial medication, whichever is of longer duration.
  • Previous enrollment or randomization in the present study (does not include screening failure).
  • Previous enrollment in the NIFE trial [AIO-YMO/HEP-0315]
  • Involvement in the planning and/or conduct of the study (applies to both Baxalta staff and/or staff of sponsor and study site)
  • Patient who might be dependent on the sponsor, site or the investigator
  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG].

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover

    Hanover, 30625

Other trials in Germany

About this study

Official title: A Randomized Phase II Trial of Nal-IRI and 5-Fluorouracil Compared to 5-Fluorouracil in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies

is an open label, randomized, multicenter phase II trial

Read the detailed description

The primary objective is to assess the efficacy of nal-IRI in gemcitabine pre-treated patients with advanced, unresectable and metastatic cholangio- and gallbladder carcinoma eligible for treatments after failure to respond to a gemcitabine-based treatment

Being tested
nal-IRI, 5-FU, leucovorin
Keywords
nal-IRI, 5-Fluorouracil

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • nal-IRIDrug

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

  • 5-FUDrug

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

  • leucovorinDrug

    leucovorin (400 mg/m2 as 0.5 hour infusion)

Study groups in NCT03043547
Study groupRoleWhat they receive
Nal-IRI + 5-FU + leucovorin (Arm A)Experimentalnal-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)
Receives: Drug: nal-IRI; Drug: 5-FU; Drug: leucovorin
5-FU + leucovorin (Arm B)OtherControl intervention/standard arm: 5-FU (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)
Receives: Drug: 5-FU; Drug: leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. progression-free survival

    Measured: approx 42 months

Secondary outcomes (4)

  1. Overall survival

    Measured: approx 42 months

  2. Objective tumor response rate (ORR) according to RECIST 1.1

    Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

    Measured: approx 42 months

  3. Toxicity/Safety

    according to Common Terminology Criteria for Adverse Events

    Measured: approx 42 months

  4. Health related Quality of Life

    EORTC QLQ-C30

    Measured: approx 42 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2017 (estimated)
  2. Study start24 Oct 2017
  3. Primary completion8 Dec 2021
  4. Study completion8 Mar 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03043547
Sponsor's protocol ID
AIO-HEP-0116
Other IDs
2016-003709-33, 2016
Acronym
NALIRICC
Status last verified
May 2022
First submitted
26 Jan 2017
Last updated
18 May 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40147791

  • 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.

    PubMed 38870977

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing nal-IRI, 5-FU and leucovorin in people with Cholangiocarcinoma Non-resectable and Cholangiocarcinoma Metastatic, run by AIO-Studien-gGmbH at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression-free survival (time frame: approx 42 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03043547, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.

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