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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04163900
Ethics application status
Date submitted
1/11/2019
Date registered
15/11/2019

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
Stopped early
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
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
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Colorado
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United States of America
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Florida
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United States of America
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Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
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United States of America
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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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State/province [18] 0 0
Washington
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United States of America
State/province [19] 0 0
Wisconsin
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
Nova Scotia
Country [22] 0 0
Canada
State/province [22] 0 0
Ontario
Country [23] 0 0
Canada
State/province [23] 0 0
Quebec
Country [24] 0 0
Czechia
State/province [24] 0 0
Brno
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Czechia
State/province [25] 0 0
Hradec Králové
Country [26] 0 0
Czechia
State/province [26] 0 0
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
State/province [30] 0 0
Levallois-Perret
Country [31] 0 0
France
State/province [31] 0 0
Paris
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France
State/province [32] 0 0
Saint Herblain
Country [33] 0 0
Germany
State/province [33] 0 0
Baden Wuerttemberg
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
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Germany
State/province [35] 0 0
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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Hungary
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Miskolc
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Hungary
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Szolnok
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Italy
State/province [42] 0 0
Genova
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Italy
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Milano
Country [44] 0 0
Italy
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Napoli
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Italy
State/province [45] 0 0
Padova
Country [46] 0 0
Italy
State/province [46] 0 0
Pisa
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Italy
State/province [47] 0 0
Verona
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Korea, Republic of
State/province [48] 0 0
Gyeonggi-do
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
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
Country [58] 0 0
Spain
State/province [58] 0 0
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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Taiwan
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Taichung
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Taiwan
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Taipei
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Turkey
State/province [63] 0 0
Adana
Country [64] 0 0
Turkey
State/province [64] 0 0
Antalya
Country [65] 0 0
Turkey
State/province [65] 0 0
Edirne
Country [66] 0 0
Turkey
State/province [66] 0 0
Istanbul
Country [67] 0 0
Turkey
State/province [67] 0 0
Malatya
Country [68] 0 0
Ukraine
State/province [68] 0 0
Chernivtsi
Country [69] 0 0
Ukraine
State/province [69] 0 0
Kharkiv
Country [70] 0 0
Ukraine
State/province [70] 0 0
Kyiv
Country [71] 0 0
Ukraine
State/province [71] 0 0
Luts'k
Country [72] 0 0
Ukraine
State/province [72] 0 0
Odesa
Country [73] 0 0
Ukraine
State/province [73] 0 0
Sumy
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Greater London
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Greater Manchester
Country [76] 0 0
United Kingdom
State/province [76] 0 0
Edinburgh
Country [77] 0 0
United Kingdom
State/province [77] 0 0
Glasgow
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Torquay
Country [79] 0 0
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT04163900