| Eligibility |
Inclusion Criteria:
1. 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
2. Age = 18 years at time of study entry
3. Histologically or cytologically confirmed, non-resectable, locally advanced or
metastatic cholangiocarcinoma or gall bladder carcinoma
4. Measurable or assessable disease according to RECIST 1.1
5. 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:
1. Single agent gemcitabine
2. Any one gemcitabine-based regimen, with or without maintenance gemcitabine
6. ECOG performance status 0-1
7. 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
8. Female patients with reproductive potential must have a negative urine or serum
pregnancy test within 7 days prior to start of treatment.
9. 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.
Exclusion Criteria:
1. 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
2. Clinically significant gastrointestinal disorder including bleeding, inflammation,
occlusion, or diarrhoea > grade 1
3. 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.
4. 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.
5. Premalignant hematologic disorders, e.g. myelodysplastic syndrome
6. Pre-existing lung disease
7. Clinically significant cardiovascular disease in (incl. myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia) 6 months before enrollment
8. History of hypersensitivity to any of the study drugs or any excipient (nal-IRI, other
liposomal products, fluoropyrimidines or leucovorin)
9. Allogeneic transplantation requiring immunosuppressive therapy or other major
immunosuppressive therapy
10. Severe non-healing wounds, ulcers or bone fractions
11. Evidence of bleeding diathesis or coagulopathy
12. 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.
13. Medication that is known to interfere with any of the agents applied in the trial.
14. 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].
15. Known Gilbert-Meulengracht syndrome
16. 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
17. 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.
18. Previous enrollment or randomization in the present study (does not include screening
failure).
19. Previous enrollment in the NIFE trial [AIO-YMO/HEP-0315]
20. Involvement in the planning and/or conduct of the study (applies to both Baxalta staff
and/or staff of sponsor and study site)
21. Patient who might be dependent on the sponsor, site or the investigator
22. Patient who has been incarcerated or involuntarily institutionalized by court order or
by the authorities § 40 Abs. 1 S. 3 Nr. 4 AMG.
23. 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].
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