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Adenocarcinoma MetastaticPhase 2NIFENCT03044587

Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer

A Phase 2 study testing Arm NaI-IRI + 5-FU + Leucovorin (Arm A) and Arm Cisplatin + Gemcitabine (Arm B) in people with Adenocarcinoma Metastatic and Biliary Tract Cancer, 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

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Trial summary

AIO-YMO/HEP-0315 (NIFE) is an open label, non-comparative, randomized, multicenter phase II trial Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Arm NaI-IRI + 5-FU + Leucovorin (Arm A) and Arm Cisplatin + Gemcitabine (Arm B)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
93 participants
Where
1 siteGermany
Study dates
24 Jan 2018to 31 Jan 2025
Phase
Phase 2

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 confirmed, non-resectable, locally advanced or metastatic adenocarcinoma of the intrahepatic or extrahepatic biliary tract
  • Protocol-specific staging guidelines have to be observed and non-resectability has to be confirmed by local tumor board
  • Measurable or assessable disease according to RECIST 1.1
  • ECOG performance status 0-1
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  • Life expectancy of more than 3 months
  • If applicable, adequately treated biliary tract obstruction before study entry with total bilirubin concentration ≤ 2 x ULN
  • Adequate blood count, liver-enzymes, and renal function:
  • White blood cell count ≥ 3.5 x 10^6/mL
  • Platelet count ≥ 100 x 10^9/L (>100,000 per mm3)
  • 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
  • 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
  • No prior palliative chemotherapy for biliary tract cancer
  • No adjuvant treatment within 6 months prior to study entry
  • Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

Who cannot join

  • Active uncontrolled infection, chronic infectious diseases, immune deficiency syndromes
  • Premalignant hematologic disorders, e.g. myelodysplastic syndrome
  • Clinically significant cardiovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before enrollment
  • Prior (>5 years) or concurrent malignancy (other than biliary-tract cancer) which either progresses or requires active treatment. Exceptions are: basal cell cancer of the skin, pre-invasive cancer of the cervix, T1a or T1b prostate carcinoma, or superficial bladder tumor [Ta, Tis and T1].
  • Pre-existing lung disease
  • History or clinical evidence of CNS metastases
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  • Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria:
  • are asymptomatic and
  • have no requirement for steroids 6 weeks prior to start of study treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases
  • History of hypersensitivity to any of the study drugs or any of the constituents of the products
  • 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 pessary (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at Screening.
  • Known Gilbert-Meulengracht syndrome
  • Known chronic hypoacusis, tinnitus or vertigo
  • 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 7 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).
  • Any other chemotherapy at study start
  • Involvement in the planning and/or conduct of the study
  • 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.
  • 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.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

About this study

Official title: Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer - An Open Label, Non-comparative, Randomized, Multicenter Phase II Trial

AIO-YMO/HEP-0315 (NIFE) is an open label, non-comparative, randomized, multicenter phase II trial

Read the detailed description

The primary objective is to determine whether a combination of 5-FU and nal-IRI prolongs progression-free survival in patients with locally advanced or metastatic adenocarcinoma of the biliary tract

Being tested
Arm NaI-IRI + 5-FU + Leucovorin (Arm A), Arm Cisplatin + Gemcitabine (Arm B)
Keywords
Biliary Tract Cancer, NaI-IRI
Medical subject headings
Biliary Tract Neoplasms, Cholangiocarcinoma, Bile Duct Neoplasms

What participants receive

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

  • Arm NaI-IRI + 5-FU + Leucovorin (Arm A)Drug

    Nal-IRI (80 mg/m2 as a 1.5 hour infusion), 5-FU (2400 mg/m2 as 46 hour infusion) and Leucovorin (400 mg/m2 as 0.5 hour infusion) Cycle q2w

  • Arm Cisplatin + Gemcitabine (Arm B)Drug

    Cisplatin (25 mg/m2 as 1 hour infusion on D1, D8) and Gemcitabine (1000 mg/m2 as 0.5 hour infusion on D1, D8) Cycle q3w

Study groups in NCT03044587
Study groupRoleWhat they receive
Arm NaI-IRI + 5-FU + Leucovorin (Arm A)ExperimentalNal-IRI [Irinotecan liposome], 5-FU [5-Fluorouracil], Leucovorin Cycle q2w
Receives: Drug: Arm NaI-IRI + 5-FU + Leucovorin (Arm A)
Arm Cisplatin + Gemcitabine (Arm B, standard of care)OtherCisplatin, Gemcitabine Cycle q3w
Receives: Drug: Arm Cisplatin + Gemcitabine (Arm B)

What is being measured

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

  1. Progression-free survival [PFS]

    Measured: approx. 25 months

Secondary outcomes (10)

  1. Overall progression free survival according to RECIST 1.1

    Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

    Measured: approx. 54 months

  2. 3-years overall survival

    3-years overall survival

    Measured: approx. 36 months

  3. Disease control rate according to RECIST 1.1

    Measured: approx. 54 months

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

    Proportion of patients with an objective response according to RECIST 1.1

    Measured: approx. 54 months

  5. Toxicity/Safety according to CTC-AE-criteria

    Measured: approx. 54 months

  6. Health related quality of life

    EORTC QLQ-BIL21

    Measured: approx. 54 months

  7. Health related quality of life

    EORTC QLQ-C30

    Measured: approx. 54 months

  8. Health related quality of life

    Hospital Anxiety and Depression Scale (HADS-D)

    Measured: approx. 54 months

  9. Retrospective correlation of resectability in accordance with a central surgical board compared to local surgical review

    Tumor resectability in accordance with a retrospective central surgical board compared to local surgical review

    Measured: approx. 54 months

  10. Retrospective central radiological review

    Measured: approx. 54 months

Timeline

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

  1. First posted7 Feb 2017 (estimated)
  2. Study start24 Jan 2018
  3. Primary completion1 Jan 2022
  4. Study completion31 Jan 2025

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
93 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03044587
Sponsor's protocol ID
AIO-YMO/HEP-0315
Other IDs
2016-002467-34, O16-33004, 2016
Acronym
NIFE
Status last verified
Sep 2025
First submitted
23 Jan 2017
Last updated
1 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ettrich TJ, Modest DP, Sinn M, Striefler JK, Opitz B, Goetze T, Gallmeier E, Angermeier S, Fischer von Weikersthal L, Jacobasch L, Waldschmidt D, Niedermeier M, Sohm M, Berger AW, Manzini G, Fehrenbach U, Auer TA, Hosse C, Vogele D, Sookthai D, Schaaf M, Muche R, Hinke A, Seufferlein T, Perkhofer L. Nanoliposomal Irinotecan With Fluorouracil and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Cholangiocarcinoma: A Phase II Study of the AIO Hepatobiliary-YMO Cancer Groups (NIFE-AIO-YMO HEP-0315). J Clin Oncol. 2024 Sep 10;42(26):3094-3104. doi: 10.1200/JCO.23.01566. Epub 2024 Jun 6.

    PubMed 38843469

  • Perkhofer L, Berger AW, Beutel AK, Gallmeier E, Angermeier S, Fischer von Weikersthal L, Goetze TO, Muche R, Seufferlein T, Ettrich TJ. Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study. BMC Cancer. 2019 Oct 23;19(1):990. doi: 10.1186/s12885-019-6142-y.

    PubMed 31646981

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