NCT03044587

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
93

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jan 2018

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 23, 2017

Completed
15 days until next milestone

First Posted

Study publicly available on registry

February 7, 2017

Completed
12 months until next milestone

Study Start

First participant enrolled

January 24, 2018

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2022

Completed
3.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2025

Completed
Last Updated

October 1, 2025

Status Verified

September 1, 2025

Enrollment Period

3.9 years

First QC Date

January 23, 2017

Last Update Submit

September 30, 2025

Conditions

Adenocarcinoma MetastaticBiliary Tract CancerAdenocarcinoma of the Biliary TractAdenocarinoma Locally AdvancedNon-Resectable Hepatocellular CarcinomaIntrahepatic Bile Duct CarcinomaExtrahepatic Bile Duct Carcinoma

Keywords

Biliary Tract CancerNaI-IRI

Outcome Measures

Primary Outcomes (1)

  • Progression-free survival [PFS]

    approx. 25 months

Secondary Outcomes (10)

  • Overall progression free survival according to RECIST 1.1

    approx. 54 months

  • 3-years overall survival

    approx. 36 months

  • Disease control rate according to RECIST 1.1

    approx. 54 months

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

    approx. 54 months

  • Toxicity/Safety according to CTC-AE-criteria

    approx. 54 months

  • +5 more secondary outcomes

Other Outcomes (3)

  • Exploratory biomarkers analysis

    approx. 54 months

  • Establishment of Predictive/Prognostic biomarker profiles for advanced cholangiocarcinoma

    approx. 54 months

  • Tumor Evolution under systemic therapy

    approx. 54 months

Study Arms (2)

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

EXPERIMENTAL

Nal-IRI \[Irinotecan liposome\], 5-FU \[5-Fluorouracil\], Leucovorin Cycle q2w

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

Arm Cisplatin + Gemcitabine (Arm B, standard of care)

OTHER

Cisplatin, Gemcitabine Cycle q3w

Drug: Arm Cisplatin + Gemcitabine (Arm B)

Interventions

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

Arm Cisplatin + Gemcitabine (Arm B, standard of care)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (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 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
  • 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
  • +2 more criteria

You may not qualify if:

  • 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
  • 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.
  • +10 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Related Publications (2)

  • 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.

    PMID: 38843469DERIVED

  • 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.

    PMID: 31646981DERIVED

Related Links

MeSH Terms

Conditions

Biliary Tract NeoplasmsCholangiocarcinomaBile Duct Neoplasms

Interventions

FluorouracilLeucovorinGemcitabine

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsBiliary Tract DiseasesDigestive System DiseasesAdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeBile Duct Diseases

Intervention Hierarchy (Ancestors)

UracilPyrimidinonesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and CoenzymesDeoxycytidineCytidinePyrimidine Nucleosides

Study Officials

  • Thomas J. Ettrich, Dr.

    Klinik für Innere Medizin I, Universitätsklinikum Ulm

    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 23, 2017

First Posted

February 7, 2017

Study Start

January 24, 2018

Primary Completion

January 1, 2022

Study Completion

January 31, 2025

Last Updated

October 1, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations

DE(1)