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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04163900




Registration number
NCT04163900
Ethics application status
Date submitted
1/11/2019
Date registered
15/11/2019
Date last updated
24/05/2023

Titles & IDs
Public title
Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer
Scientific title
A Phase III Open-Label, Multi-Centre, Randomized Study Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Previously Untreated Locally Advanced or Metastatic Biliary Tract Cancer
Secondary ID [1] 0 0
2019-001025-28
Secondary ID [2] 0 0
NuTide:121
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Biliary Tract Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NUC-1031
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Cisplatin

Experimental: A - NUC-1031 and cisplatin - 725 mg/m^2 NUC-1031 administered in combination with 25 mg/m^2 cisplatin on Days 1 and 8 of a 21-day cycle

Active Comparator: B - gemcitabine and cisplatin - 1000 mg/m^2 gemcitabine administered in combination with 25 mg/m^2 cisplatin on Days 1 and 8 of a 21-day cycle


Treatment: Drugs: NUC-1031
IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes

Treatment: Drugs: Gemcitabine
IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert

Treatment: Drugs: Cisplatin
IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
Evaluated at Screening (baseline) then every 9 weeks from treatment start (C1D1), or every 12 weeks if treatment is stopped with no evidence of progression, until disease progression or death from any cause up to the end of study, an average of 6 months.
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From the date of randomization until the date of death from any cause, assessed up to 12 months on average

Eligibility
Key inclusion criteria
1. Written informed consent and authorization 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 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. Eastern Cooperative Oncology Group (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.

- Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) <5 × ULN

- Creatinine clearance =45 mL/min actual or calculated by the Cockcroft-Gault
method

- International normalized 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.

10. Human Immunodeficiency Virus-infected patients who are healthy and have a low risk of
Acquired Immunodeficiency Syndrome-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
sterilization) 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 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 partner meet the criteria above (not of childbearing potential
or practicing highly effective contraceptive methods).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Combined or mixed hepatocellular/cholangiocarcinoma.

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-sensitizing low-dose
chemotherapy) for localized disease and there is now clear evidence of disease
progression requiring systemic chemotherapy.

- Photodynamic therapy: prior photodynamic therapy for localized disease with no
evidence of metastatic disease or for localized 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 adverse events
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 non-melanoma 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 of
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 other co-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 randomization.

10. Major surgery within 28 days prior to randomization; patient must have completely
recovered from any prior surgical or other procedures.

11. Pregnant or breastfeeding.

12. Residual toxicities from prior treatments or procedures which have not regressed to
Grade =1 severity (CTCAE v5.0), except for alopecia or = Grade 2 peripheral
neuropathy.

13. Concomitant use of drugs at doses known to cause clinically relevant prolongation of
QT/QTc interval.

14. Administration of a live vaccination within 28 days prior to randomization.

15. Ongoing or recent (=6 months) hepatorenal syndrome.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
24/12/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/04/2022
Sample size
Target
Accrual to date
Final
773
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
St George Hospital - Kogarah
Recruitment hospital [3] 0 0
Newcastle Private Hospital - Newcastle
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment hospital [5] 0 0
Townsville Cancer Centre - Townsville
Recruitment hospital [6] 0 0
Warringal Medical Centre - Heidelberg
Recruitment hospital [7] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [8] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [9] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2217 - Kogarah
Recruitment postcode(s) [3] 0 0
2305 - Newcastle
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment postcode(s) [5] 0 0
4814 - Townsville
Recruitment postcode(s) [6] 0 0
3084 - Heidelberg
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
6150 - Murdoch
Recruitment postcode(s) [9] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
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Arizona
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United States of America
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California
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Colorado
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Florida
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Georgia
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United States of America
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Illinois
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United States of America
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Kansas
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United States of America
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Kentucky
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Massachusetts
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Michigan
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Minnesota
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New York
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North Carolina
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Ohio
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Pennsylvania
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South Carolina
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Texas
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Washington
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United States of America
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Wisconsin
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Canada
State/province [20] 0 0
Alberta
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Czechia
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Brno
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Czechia
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Hradec Králové
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Czechia
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Olomouc
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Czechia
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Prague
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France
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Dijon
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France
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Grenoble
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France
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Levallois-Perret
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France
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Paris
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France
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Saint Herblain
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Germany
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Baden Wuerttemberg
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Germany
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Berlin
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Germany
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Freiburg
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Germany
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Hanover
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Germany
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Tuebingen
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Hungary
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Budapest
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Hungary
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Debrecen
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Miskolc
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Hungary
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Szolnok
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Italy
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Genova
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Italy
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Milano
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Italy
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Napoli
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Italy
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Padova
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Italy
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Pisa
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Italy
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Verona
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Jeollanam-do
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Korea, Republic of
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Pusan
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Korea, Republic of
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Seongnam-si
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Korea, Republic of
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Seoul
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Russian Federation
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Tyumen
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Spain
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Barcelona
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Spain
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L'Hospitalet De Llobregat
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Spain
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Madrid
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Spain
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Sevilla
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Taiwan
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Changhua
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Taichung
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Taipei
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Turkey
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Adana
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Antalya
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Edirne
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Turkey
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Istanbul
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Turkey
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Malatya
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Ukraine
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Chernivtsi
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Ukraine
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Kharkiv
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Ukraine
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Kyiv
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Ukraine
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Luts'k
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Ukraine
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Odesa
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Ukraine
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Sumy
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United Kingdom
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Greater London
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United Kingdom
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Greater Manchester
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Edinburgh
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United Kingdom
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Glasgow
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United Kingdom
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Torquay
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United Kingdom
State/province [79] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Other
Name
NuCana plc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
NuTide:121 compares NUC-1031 with gemcitabine, both in combination with cisplatin, in
patients with previously untreated advanced biliary tract cancer.

The primary hypotheses are:

- The combination of NUC-1031 plus cisplatin prolongs overall survival compared to the
gemcitabine plus cisplatin standard of care

- The combination of NUC-1031 plus cisplatin increases overall response rate compared to
the gemcitabine plus cisplatin standard of care
Trial website
https://clinicaltrials.gov/ct2/show/NCT04163900
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jennifer Knox, MD
Address 0 0
Professor of Medicine, University of Toronto
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04163900