Nal-IRI and 5-FU Compared to 5-FU in Patients With Cholangio- and Gallbladder Carcinoma Previously Treated With Gemcitabine-based Therapies (NALIRICC)
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|ClinicalTrials.gov Identifier: NCT03043547|
Recruitment Status : Completed
First Posted : February 6, 2017
Last Update Posted : May 18, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Cholangiocarcinoma Non-resectable Cholangiocarcinoma Metastatic Cholangiocarcinoma of the Gallbladder Cholangiocarcinoma Advanced||Drug: nal-IRI Drug: 5-FU Drug: leucovorin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||100 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||October 24, 2017|
|Actual Primary Completion Date :||December 8, 2021|
|Actual Study Completion Date :||March 8, 2022|
Experimental: Nal-IRI + 5-FU + leucovorin (Arm A)
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)
nal-IRI [Irinotecan liposome] (80 mg/m2 as a 1.5 hour infusion)
5-FU [5-Fluorouracil] (2400 mg/m2 as 46 hour infusion)
leucovorin (400 mg/m2 as 0.5 hour infusion)
5-FU + leucovorin (Arm B)
Control intervention/standard arm: 5-FU (2400 mg/m2 as 46 hour infusion) and leucovorin (400 mg/m2 as 0.5 hour infusion) (q2w)
5-FU [5-Fluorouracil] (2400 mg/m2 as 46 hour infusion)
leucovorin (400 mg/m2 as 0.5 hour infusion)
- progression-free survival [ Time Frame: approx 42 months ]
- Overall survival [ Time Frame: approx 42 months ]
- Objective tumor response rate (ORR) according to RECIST 1.1 [ Time Frame: approx 42 months ]Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)
- Toxicity/Safety [ Time Frame: approx 42 months ]according to Common Terminology Criteria for Adverse Events
- Health related Quality of Life [ Time Frame: approx 42 months ]EORTC QLQ-C30
- biomarkers [ Time Frame: approx 42 months ]Ca-19-9, CEA, CRP serum levels
- Immunohistochemistry of Carboxylesterase (CES) [ Time Frame: approx 42 months ]
- Analyse whole blood [ Time Frame: approx 42 months ]will be collected to potentially identify factors that may correlate with tumour response, sensitivity or resistance to nal-IRI
- Analyse plasma [ Time Frame: approx 42 months ]will be collected to potentially identify factors that may correlate with tumour response, sensitivity or resistance to nal-IRI
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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
- 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.
- 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
- 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].
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03043547
|Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover|
|Hannover, Germany, 30625|
|Principal Investigator:||Arndt Vogel, Prof.||Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover|
|Other Study ID Numbers:||
2016-003709-33 ( EudraCT Number )
|First Posted:||February 6, 2017 Key Record Dates|
|Last Update Posted:||May 18, 2022|
|Last Verified:||May 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||No|
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