Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer

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

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

Study Overview

• Status: Terminated
• Conditions: Biliary Tract Cancer
• Intervention / Treatment: Drug: NUC-1031; Drug: Cisplatin; Drug: Gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 773
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Kogarah, New South Wales, Australia, 2217
      • St George Hospital
    • Newcastle, New South Wales, Australia, 2305
      • Newcastle Private Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • Townsville, Queensland, Australia, 4814
      • Townsville Cancer Centre
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Warringal Medical Centre
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H1V7
      • Nova Scotia Health Authority
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute
    • Toronto, Ontario, Canada, M5G 1X6
      • Princess Margaret Cancer Centre
  • Quebec
    • Montréal, Quebec, Canada, H3T 1E2
      • SMBD Jewish General Hospital
    • Montréal, Quebec, Canada, H2X 0A9
      • CHUM Centre de Recherche
• Czechia
  • Brno, Czechia, 625 00
    • Fakultní Nemocnice Brno
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Olomouc, Czechia, 775 20
    • Fakultni Nemocnice Olomouc
  • Prague, Czechia, 150 30
    • Nemocnice Na Homolce
  • Prague, Czechia, 140 59
    • Thomayerova nemocnice
• France
  • Dijon, France, 21079
    • Centre Georges Francois Leclerc
  • Grenoble, France, 38043
    • CHU de Grenoble - Hôpital Nord
  • Levallois-Perret, France, 92300
    • Institut Hospitalier Franco-Britannique
  • Paris, France, 75679
    • Hôpital COCHIN
  • Saint Herblain, France, 44805
    • ICO - Site René Gauducheau
• Germany
  • Berlin, Germany, 12351
    • Vivantes Klinikum Neukoelln
  • Freiburg, Germany, 79106
    • Universitaetsklinikum Freiburg
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Tuebingen, Germany, 72076
    • Universitaetsklinikum Tuebingen
  • Baden Wuerttemberg
    • Heidelberg, Baden Wuerttemberg, Germany, 69120
      • Universitaetsklinikum Heidelberg
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem
  • Miskolc, Hungary, 3526
    • Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz
  • Szolnok, Hungary, 5004
    • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelointézet
• Italy
  • Genova, Italy, 16132
    • Ospedale Policlinico San Martino
  • Milano, Italy, 20141
    • IEO Istituto Europeo di Oncologia
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori Fondazione G. Pascale
  • Padova, Italy, 35128
    • Iov - Istituto Oncologico Veneto Irccs
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Verona, Italy, 37124
    • Centro Ricerche Cliniche di Verona S.r.l
• Korea, Republic of
  • Pusan, Korea, Republic of, 602-715
    • Dong-A University Hospital
  • Seongnam-si, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital, Yonsei University
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 08308
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
      • CHA Bundang Medical Center, CHA University
  • Jeollanam-do
    • Hwasun, Jeollanam-do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital
• Russian Federation
  • Moscow, Russian Federation, 115478
    • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
  • Moscow, Russian Federation, 115478
    • FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin
  • Moscow, Russian Federation, 129515
    • "VitaMed" LLC
  • Saint Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • Saint Petersburg, Russian Federation, 191104
    • State Budget Institution of Healthcare "Leningrad Regional Clinical Oncology Dispensary"
  • Saint Petersburg, Russian Federation, 197022
    • SPb SBIH "City Clinical Oncological Dispensary"
  • Tyumen, Russian Federation, 625041
    • Medicinskiy gorod
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • L'Hospitalet De Llobregat, Spain, 08908
    • ICO l'Hospitalet - Hospital Duran i Reynals
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain, 28050
    • Hospital Universitario HM Madrid Sanchinarro
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
• Taiwan
  • Changhua, Taiwan, 50004
    • Changhua Christian Medical Foundation Changhua Christian Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10016
    • National Taiwan University Hospital
  • Taipei, Taiwan, 10449
    • MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hospital
  • Adana, Turkey, 01220
    • Baskent University Adana Application and Research Center
  • Antalya, Turkey, 07058
    • Akdeniz University Medical Faculty
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey, 34098
    • Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
  • Malatya, Turkey, 06105
    • Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
  • Malatya, Turkey, 44280
    • Inonu University Medical Facility
• Ukraine
  • Chernivtsi, Ukraine, 58013
    • CI Chernivtsi RC Oncological Dispensary
  • Kharkiv, Ukraine, 61166
    • CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
  • Kharkiv, Ukraine, 61070
    • Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Oncological Center
  • Kyiv, Ukraine, 03126
    • SI "Shalimov's National Institute of Surgery and Transplantation" of NAMSU
  • Luts'k, Ukraine, 43018
    • Treatment-Prevention Institution Volyn Regional Oncological Dispensary
  • Odesa, Ukraine, 65025
    • Communal Institution Odesa Regional Clinical Hospital
  • Sumy, Ukraine, 40022
    • RCI Sumy Regional Clinical Oncological Dispensary
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Glasgow, United Kingdom, G12 OYN
    • Beatson West of Scotland Cancer Centre
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital
  • Wirral, United Kingdom, CH63 4JY
    • The Clatterbridge Cancer Centre
  • Greater London
    • London, Greater London, United Kingdom, SE1 9RY
      • Guy's Hospital
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M20 4BX
      • The Christie
• United States
  • Arizona
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates , PC - HOPE
  • California
    • Whittier, California, United States, 90602-3171
      • The Oncology Institute of Hope and Innovation
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers, LLP- Aurora
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist Health Medical Group Oncology, LLC
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc.
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Iact Health
  • Illinois
    • Chicago Ridge, Illinois, United States, 60415
      • Affiliated Oncologists LLC
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center Research Institute, Inc.
  • Kentucky
    • Louisville, Kentucky, United States, 40217
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215-5400
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Group
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Regents of the University of Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hemtology
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center - Strong Memorial Hospital
    • Stony Brook, New York, United States, 11794-3369
      • The Research Foundation for the State University of New York
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University James Cancer Hospital and Solove Research Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Corporal Michael J. Crescenz VA Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Upstate
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology, P.A. - Austin
    • Dallas, Texas, United States, 75246
      • Baylor Charles A. Sammons Cancer Center
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research and Treatment Center
    • Tyler, Texas, United States, 75702
      • Texas Oncology, P.A. - Tyler
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists, P.C.-Vancouver
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • The Medical College of Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Drug: NUC-1031; IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes; Other Names: fosgemcitabine palabenamide; Drug: Cisplatin; IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol; Other Names: CDDP
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	Drug: Cisplatin; IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol; Other Names: CDDP; Drug: Gemcitabine; IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert; Other Names: Gemzar; Difluorodeoxycytidine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Percentage of patients achieving a confirmed complete response (CR) or partial response (PR) to treatment as assessed by blinded independent review according to RECIST v1.1 criteria. ORR = patients with CR + patients with PR, where" CR = disappearance of all target lesions PR = at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters This outcome was assessed in the population of patients with measurable disease at baseline who were also randomized ≥28 weeks before the data cut-off (ITTMD28). Patients were to receive a confirmatory scan 28-42 days after response is first observed.	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.
Overall Survival (OS)	The median time, in months, from the date of randomization to the date of death from any cause. For patients who were alive at the time of a data cut-off or were permanently lost to follow up, duration of OS was censored at the date at which they were last known to be alive.	From the date of randomization until the date of death from any cause, assessed up to 12 months on average

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Based on blinded independent review according to RECIST v1.1 criteria and defined as the time from randomization to the first observation of objective tumour progression or death from any cause	Evaluated every 9 weeks from start of treatment or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment
Duration of response (DoR)	Defined as the time from initial clinical response to the first observation of tumour progression or death from any cause as assessed by blinded independent review	Evaluated every 9 weeks from initial clinical response or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment
12-month survival	Proportion of patients still alive at 12 months from randomization	12 months from randomization
18-month survival	Proportion of patients still alive at 18 months from randomization	18 months from randomization
Disease control rate (DCR)	Based on blinded independent review according to RECIST v1.1, defined as the percentage of patients demonstrating a Best Overall Response of Complete Response, Partial Response or Stable Disease	Evaluated every 9 weeks from start of treatment or, where treatment is stopped with no evidence of progression, every 12 weeks until disease progression or death from any cause, up to a maximum of 18 months after the last patient starts treatment
Safety and tolerability	Safety and tolerability will be assessed by total incidence of Treatment Emergent Adverse Events (TEAEs) according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Adverse events that occur from initiation of therapy until 30 day post-treatment will be recorded. Adverse events that are not resolved at this time will be followed until resolution to baseline value.
Maximum observed plasma concentration (Cmax) of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only		Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)
Area under the plasma concentration-time curve (AUC) of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only		Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)
Elimination half-life (t½) of NUC-1031, dFdC and dFdU using descriptive statistics in Arm A only		Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)
Terminal elimination rate constant (λz) of NUC-1031, dFdC and dFdU using descriptive statistics in Arm A only		Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)
Clearance of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only		Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)
Volume of distribution of NUC-1031, dFdC and dFdU will be compared to existing data using simulations in Arm A only		Day 1 of Cycle 1 (each cycle is 21 days): Blood samples taken within 10 minutes post-end of infusion, 2 hours post-end of infusion (±30 minutes) and 6 hours post-end of infusion (±30 minutes)
Comparison of patient-reported quality of life (QoL) scores in Arm A and Arm B	Assessed using the European Organisation for Research and Treatment (EORTC) Quality of Life Questionnaire (QLQ-C30) using the QLQ-BIL21 module	Assessed at screening, on Day 1 of every cycle (each cycle is 21 days), and 30 days post-treatment
Comparison of patient-reported quality of life (QoL) scores in Arm A and Arm B	Assessed using the 5-level EuroQol five-dimension scale (EQ-5D-5L)	Assessed at screening, on Day 1 of every cycle (each cycle is 21 days), and 30 days post-treatment

Collaborators and Investigators

• Sponsor: NuCana plc
• Investigators: Principal Investigator: Jennifer Knox, MD, Professor of Medicine, University of Toronto

Publications and helpful links

General Publications

• McNamara MG, Goyal L, Doherty M, Springfeld C, Cosgrove D, Sjoquist KM, Park JO, Verdaguer H, Braconi C, Ross PJ, Gramont A, Zalcberg JR, Palmer DH, Valle JW, Knox JJ. NUC-1031/cisplatin versus gemcitabine/cisplatin in untreated locally advanced/metastatic biliary tract cancer (NuTide:121). Future Oncol. 2020 Jun;16(16):1069-1081. doi: 10.2217/fon-2020-0247. Epub 2020 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2019
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): April 5, 2022

Study Registration Dates

• First Submitted: November 1, 2019
• First Submitted That Met QC Criteria: November 12, 2019
• First Posted (Actual): November 15, 2019

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Gemcitabine; Cisplatin; Adenocarcinoma; Metastatic; Chemotherapy; Antineoplastic Agents; Cholangiocarcinoma; Gallbladder; Biliary Tract Cancer; Gastrointestinal; Neoplasm; Locally advanced; Untreated; Digestive System Neoplasms; Hepatobiliary; Intrahepatic; Ampullary; Distal Bile Duct; Extrahepatic; First-line Chemotherapy; NUC-1031; ProTides
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: NuTide:121; 2019-001025-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No