Study Stopped
A pre-planned futility analysis concluded that NUC-1031 plus cisplatin was unlikely to achieve its primary objective of improving overall survival. Based on the IDMC's recommendation, NuCana has closed the study.
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
2 other identifiers
interventional
773
15 countries
125
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 Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2019
125 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 1, 2019
CompletedFirst Posted
Study publicly available on registry
November 15, 2019
CompletedStudy Start
First participant enrolled
December 24, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 2, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
April 5, 2022
CompletedResults Posted
Study results publicly available
May 24, 2023
CompletedMay 24, 2023
May 1, 2023
2.2 years
November 1, 2019
March 2, 2023
May 22, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
Study Arms (2)
A - NUC-1031 and cisplatin
EXPERIMENTAL725 mg/m\^2 NUC-1031 administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle
B - gemcitabine and cisplatin
ACTIVE COMPARATOR1000 mg/m\^2 gemcitabine administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle
Interventions
IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes
IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert
IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol
Eligibility Criteria
You may qualify if:
- Written informed consent and authorization to use and disclose health information.
- Ability to comprehend and willingness to comply with the requirements of this protocol, including the QoL questionnaires.
- Female or male patients aged ≥18 years.
- 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.
- Life expectancy ≥16 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- 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
- 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.
- 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.
- 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.
- +2 more criteria
You may not qualify if:
- Combined or mixed hepatocellular/cholangiocarcinoma.
- 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.
- 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).
- Symptomatic central nervous system or leptomeningeal metastases.
- 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.
- 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.
- 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.
- Prior exposure to another investigational agent within 28 days prior to randomization.
- Major surgery within 28 days prior to randomization; patient must have completely recovered from any prior surgical or other procedures.
- Pregnant or breastfeeding.
- 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.
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- NuCana plclead
Study Sites (125)
Arizona Oncology Associates , PC - HOPE
Tucson, Arizona, 85711, United States
University of Arizona Cancer Center
Tucson, Arizona, 85719, United States
The Oncology Institute of Hope and Innovation
Whittier, California, 90602-3171, United States
Rocky Mountain Cancer Centers, LLP- Aurora
Aurora, Colorado, 80012, United States
Baptist Health Medical Group Oncology, LLC
Miami, Florida, 33176, United States
Orlando Health, Inc.
Orlando, Florida, 32806, United States
IACT Health
Columbus, Georgia, 31904, United States
Affiliated Oncologists LLC
Chicago Ridge, Illinois, 60415, United States
University of Kansas Medical Center Research Institute, Inc.
Westwood, Kansas, 66205, United States
Norton Cancer Institute
Louisville, Kentucky, 40217, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215-5400, United States
Henry Ford Medical Group
Detroit, Michigan, 48202, United States
Minnesota Oncology Hemtology
Minneapolis, Minnesota, 55404, United States
Regents of the University of Minnesota
Minneapolis, Minnesota, 55455, United States
University of Rochester Medical Center - Strong Memorial Hospital
Rochester, New York, 14642, United States
The Research Foundation for The State University of New York
Stony Brook, New York, 11794-3369, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
The Ohio State University James Cancer Hospital and Solove Research Institute
Columbus, Ohio, 43210, United States
Corporal Michael J. Crescenz VA Medical Center
Philadelphia, Pennsylvania, 19104, United States
Prisma Health Upstate
Greenville, South Carolina, 29605, United States
Texas Oncology, P.A. - Austin
Austin, Texas, 78705, United States
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246, United States
Joe Arrington Cancer Research and Treatment Center
Lubbock, Texas, 79410, United States
Texas Oncology, P.A. - Tyler
Tyler, Texas, 75702, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
Northwest Cancer Specialists, P.C.-Vancouver
Vancouver, Washington, 98684, United States
Wenatchee Valley Hospital and Clinics
Wenatchee, Washington, 98801, United States
The Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53226, United States
Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
St George Hospital
Kogarah, New South Wales, 2217, Australia
Newcastle Private Hospital
Newcastle, New South Wales, 2305, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Townsville Cancer Centre
Townsville, Queensland, 4814, Australia
Warringal Medical Centre
Heidelberg, Victoria, 3084, Australia
The Alfred Hospital
Melbourne, Victoria, 3004, Australia
Fiona Stanley Hospital
Murdoch, Western Australia, 6150, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Nova Scotia Health Authority
Halifax, Nova Scotia, B3H1V7, Canada
Royal Victoria Regional Health Centre
Barrie, Ontario, L4M 6M2, Canada
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
Sunnybrook Research Institute
Toronto, Ontario, M4N 3M5, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1X6, Canada
CHUM Centre de Recherche
Montreal, Quebec, H2X 0A9, Canada
SMBD Jewish General Hospital
Montreal, Quebec, H3T 1E2, Canada
Fakultní nemocnice Brno
Brno, 625 00, Czechia
Fakultní nemocnice Hradec Králové
Hradec Králové, 500 05, Czechia
Fakultní nemocnice Olomouc
Olomouc, 775 20, Czechia
Thomayerova nemocnice
Prague, 140 59, Czechia
Nemocnice Na Homolce
Prague, 150 30, Czechia
Centre Georges François Leclerc
Dijon, 21079, France
CHU de Grenoble - Hôpital Nord
Grenoble, 38043, France
Institut Hospitalier Franco-Britannique
Levallois-Perret, 92300, France
Hôpital Cochin
Paris, 75679, France
ICO - Site René Gauducheau
Saint-Herblain, 44805, France
Universitaetsklinikum Heidelberg
Heidelberg, Baden-Wurttemberg, 69120, Germany
Vivantes Klinikum Neukoelln
Berlin, 12351, Germany
Universitaetsklinikum Freiburg
Freiburg im Breisgau, 79106, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Universitaetsklinikum Tuebingen
Tübingen, 72076, Germany
Semmelweis Egyetem
Budapest, 1083, Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
Budapest, 1097, Hungary
Orszagos Onkologiai Intezet
Budapest, 1122, Hungary
Debreceni Egyetem
Debrecen, 4032, Hungary
Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz
Miskolc, 3526, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
Szolnok, 5004, Hungary
Ospedale Policlinico San Martino
Genova, 16132, Italy
IEO Istituto Europeo di Oncologia
Milan, 20141, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
Napoli, 80131, Italy
IOV - Istituto Oncologico Veneto IRCCS
Padua, 35128, Italy
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126, Italy
Centro Ricerche Cliniche di Verona S.r.l
Verona, 37124, Italy
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
Moscow, 115478, Russia
FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin
Moscow, 115478, Russia
"VitaMed" LLC
Moscow, 129515, Russia
State Budget Institution of Healthcare "Leningrad Regional Clinical Oncology Dispensary"
Saint Petersburg, 191104, Russia
Pavlov First Saint Petersburg State Medical University
Saint Petersburg, 197022, Russia
SPb SBIH "City Clinical Oncological Dispensary"
Saint Petersburg, 197022, Russia
Medicinskiy gorod
Tyumen, 625041, Russia
CHA Bundang Medical Center, CHA University
Seongnam-si, Gyeonggi-do, 13496, South Korea
Chonnam National University Hwasun Hospital
Hwasun, Jeollanam-do, 58128, South Korea
Dong-A University Hospital
Pusan, 602-715, South Korea
Seoul National University Bundang Hospital
Seongnam-si, 13620, South Korea
Korea University Anam Hospital
Seoul, 02841, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
Korea University Guro Hospital
Seoul, 08308, South Korea
Severance Hospital, Yonsei University
Seoul, 3722, South Korea
Asan Medical Center
Seoul, 5505, South Korea
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Clinic de Barcelona
Barcelona, 08036, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
L'Hospitalet de Llobregat, 08908, Spain
Hospital General Universitario Gregorio Marañon
Madrid, 28007, Spain
Hospital Universitario Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario HM Madrid Sanchinarro
Madrid, 28050, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Hospital Universitario Virgen del Rocio
Seville, 41013, Spain
Changhua Christian Medical Foundation Changhua Christian Hospital
Changhua, 50004, Taiwan
China Medical University Hospital
Taichung, 40447, Taiwan
National Taiwan University Hospital
Taipei, 10016, Taiwan
MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital
Taipei, 10449, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Acibadem Adana Hospital
Adana, 01130, Turkey (Türkiye)
Baskent University Adana Application and Research Center
Adana, 01220, Turkey (Türkiye)
Akdeniz University Medical Faculty
Antalya, 07058, Turkey (Türkiye)
Trakya University Medical Faculty
Edirne, 22030, Turkey (Türkiye)
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
Istanbul, 34098, Turkey (Türkiye)
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
Malatya, 06105, Turkey (Türkiye)
Inonu University Medical Facility
Malatya, 44280, Turkey (Türkiye)
CI Chernivtsi RC Oncological Dispensary
Chernivtsi, 58013, Ukraine
Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU
Kharkiv, 61070, Ukraine
CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
Kharkiv, 61166, Ukraine
Kyiv City Clinical Oncological Center
Kyiv, 03115, Ukraine
SI "Shalimov's National Institute of Surgery and Transplantation" of NAMSU
Kyiv, 03126, Ukraine
Treatment-Prevention Institution Volyn Regional Oncological Dispensary
Lutsk, 43018, Ukraine
Communal Institution Odesa Regional Clinical Hospital
Odesa, 65025, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
Sumy, 40022, Ukraine
Guy's Hospital
London, Greater London, SE1 9RY, United Kingdom
The Christie
Manchester, Greater Manchester, M20 4BX, United Kingdom
Western General Hospital
Edinburgh, EH4 2XU, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 OYN, United Kingdom
The Clatterbridge Cancer Centre
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Torbay Hospital
Torquay, TQ2 7AA, United Kingdom
Related Publications (2)
Knox JJ, McNamara MG, Bazin IS, Oh DY, Zubkov O, Breder V, Bai LY, Christie A, Goyal L, Cosgrove DP, Springfeld C, Sjoquist KM, Park JO, Verdaguer H, Braconi C, Ross PJ, De Gramont A, Shroff RT, Zalcberg JR, Palmer DH, Smith JR, Oelmann E, Bruce T, Valle JW. A phase III randomized study of first-line NUC-1031/cisplatin vs. gemcitabine/cisplatin in advanced biliary tract cancer. J Hepatol. 2025 Aug;83(2):358-366. doi: 10.1016/j.jhep.2025.01.040. Epub 2025 Feb 18.
PMID: 39978598DERIVEDMcNamara 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.
PMID: 32374623DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
At Interim Analysis 1, the futility boundary for OS was crossed and the study was closed on 02 Mar 2022. Following study closure, data from the 05 April 2022 final data cut-off (30 day follow-up post the last patient last visit) were analysed. In general, the analyses performed on this final database were those that were scheduled to take place at Interim Analysis 2. However, any p-values or CIs obtained are only viewed as descriptive as the study was stopped for futility.
Results Point of Contact
- Title
- Medical and Scientific Affairs Department
- Organization
- NuCana plc
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer Knox, MD
Professor of Medicine, University of Toronto
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Masking Details
- Imaging scans will be assessed by blinded independent review according to RECIST v1.1
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 1, 2019
First Posted
November 15, 2019
Study Start
December 24, 2019
Primary Completion
March 2, 2022
Study Completion
April 5, 2022
Last Updated
May 24, 2023
Results First Posted
May 24, 2023
Record last verified: 2023-05
Data Sharing
- IPD Sharing
- Will not share