A study of NUC-1031 plus Cisplatin versus Gemcitabine plus Cisplatin in Previously Untreated Biliary Tract Cancer
- Conditions
- Histologically- or cytologically-confirmed adenocarcinoma of the biliary tract (including gallbladder, intra and extra-hepatic biliary ducts and ampullary [pancreaticobiliary subtype onlysee exclusion criterion 1] cancers) that is locally advanced, unresectable or metastatic (AJCC edition 8, 2018).Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001025-28-DE
- Lead Sponsor
- uCana plc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 828
1. Written informed consent and authorisation to use and disclose health information.
2. Ability to comprehend and willingness to comply with the requirements of this protocol, including the QoL questionnaires.
3. Female or male patients aged =18 years.
4. Histologically- or cytologically-confirmed adenocarcinoma of the biliary tract (including gallbladder, intra and extra-hepatic biliary ducts and ampullary [pancreaticobiliary subtype only; see exclusion criterion 1] cancers) that is locally advanced, unresectable or metastatic (AJCC edition 8, 2018). Patients with measurable (as per RECIST v1.1 criteria) or non-measurable disease are permitted.
5. Life expectancy =16 weeks.
6. ECOG performance status 0 or 1.
7. Adequate biliary drainage with no evidence of ongoing infection. If applicable, treatable and clinically-relevant biliary duct obstruction has been relieved by internal endoscopic drainage/stenting at least 2 weeks previously or by palliative bypass surgery or percutaneous drainage prior to study treatment, and the patient has no active or suspected uncontrolled infection. Patients fitted with a biliary stent should be clinically stable and free of signs of infection for =2 weeks prior to study treatment. Patients with improving biliary function who meet all other inclusion criteria may be re-tested during the screening window.
8. Adequate bone marrow, hepatic, and renal function, as evidenced by:
• Absolute neutrophil count (ANC) =1,500/µL without colony-stimulating factor support.
• Platelet count =100,000/µL.
• Haemoglobin =9 g/dL without need for haematopoietic growth factor or transfusion support in prior 2 weeks.
• Total bilirubin <2 × upper limit of normal (ULN); does not apply to patients with Gilbert's syndrome. Consistent with inclusion criterion 7, patients whose whole bilirubin and biliary function is recovering may be re-tested during the screening period.
• ALT and/or AST <5 × ULN
• Creatinine clearance =45 mL/min actual or calculated by the Cockcroft-Gault method.
• International normalised ratio (INR) <1.5 and activated partial thromboplastin time (aPTT) <1.5 × ULN; does not apply to patients on an anti-coagulant with stable dose 28 days prior to first dose.
9. QTc interval <450 msec (males) or <470 msec (females), in the absence of bundle branch block. In the presence of bundle branch block with consequent QTc prolongation, patients may be enrolled based on a careful risk-benefit assessment. Patients with the presence of bundle branch block for whom a QT calculation cannot be reliably determined should not be included.
10. Human Immunodeficiency Virus (HIV)-infected patients who are healthy and have a low risk of Acquired Immune Deficiency Syndrome-(AIDS) related outcomes may be included in this study.
11. Female patients of child-bearing potential (i.e., all women except those who are post-menopausal for =1 year or who have a history of hysterectomy or surgical sterilisation) must have a negative pregnancy test within 3 days prior to the first study drug administration. All patients of child-bearing potential must agree to practice true abstinence or to use two highly effective forms of contraception, one of which must be a barrier method and one of which must be a highly effective form of contraception, from the time of screening until 6 months after the last dose of study medication.
12. Male patients with a female partner must either have had a successful vasectomy or they and their female partn
1. Combined or mixed hepatocellular/cholangiocarcinoma or ampullary cancer of the intestinal
or mixed subtypes.
2. Prior systemic therapy for advanced or metastatic biliary tract cancer. However, prior
chemotherapy in the adjuvant setting or low-dose chemotherapy given in conjunction with
radiotherapy in the adjuvant setting and completed at least 6 months prior to enrolment is
permitted. The following prior interventions are allowed provided the patient has fully
recovered:
• Surgery: non-curative resection with macroscopic residual disease or palliative bypass surgery.
Patients who have previously undergone curative surgery must now have evidence of
non-resectable disease requiring systemic chemotherapy.
• Radiotherapy: prior radiotherapy (with or without radio-sensitising low-dose chemotherapy)
for localised disease and there is now clear evidence of disease progression requiring systemic
chemotherapy.
• Photodynamic therapy: prior photodynamic therapy for localised disease with no evidence of
metastatic disease or for localised disease to relieve biliary obstruction in the presence of
metastatic disease provided there is now clear evidence of disease progression requiring
systemic chemotherapy.
• Palliative radiotherapy: palliative radiotherapy provided that all AEs have resolved and the
patient has measurable disease outside the field of radiation.
3. Prior treatment with or known hypersensitivity to NUC-1031,
gemcitabine, cisplatin or other platinum-based agents or history of
allergic reactions attributed to any parenteral excipients (e.g.,
dimethylacetamide [DMA], Cremophor EL, Polysorbate 80, Solutol HS
15).
4. Symptomatic central nervous system or leptomeningeal metastases.
5. History of other malignancies, except adequately treated nonmelanoma
skin cancer, curatively treated in situ cancer of the cervix,
surgically excised or potentially curatively treated ductal carcinoma in
situ of the breast, or low grade prostate cancer or patients after
prostatectomy not requiring treatment. Patients with previous invasive
cancers are eligible if treatment was completed more than 3 years prior
to initiating the current study treatment, and the patient has had no
evidence or recurrence since then.
6. Concurrent serious (as deemed by the Investigator) medical conditions, including, but not
limited to, New York Heart Association class III or IV congestive heart failure, history of
congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C, or otherco-morbid conditions that in the opinion of the Investigator would impair study participation
or cooperation.
7. Congenital or acquired immunodeficiency (e.g., serious active infection with HIV). As per
inclusion criterion 10, patients with HIV who are healthy and have a low risk of AIDS-related
outcomes are eligible.
8. Other acute or chronic medical, neurological, or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or investigational
product administration or may interfere with the interpretation of study results and, in the
judgment of the investigator, would make the patient inappropriate for entry into this study.
9. Prior exposure to another investigational agent within 28 days prior to randomisation.
10. Major surgery within 28 days prior to randomisation; patient must have completely recovered
from any prior surgical or other procedures.
11. Pregnant or breastfeeding.
12. Residual toxicities fro
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method