Comparing NUC-1031 Plus Cisplatin to Gemcitabine Plus Cisplatin in Patients With Advanced Biliary Tract Cancer
- Conditions
- Biliary Tract Cancer
- Interventions
- Registration Number
- NCT04163900
- Lead Sponsor
- NuCana plc
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 773
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Written informed consent and authorization to use and disclose health information.
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Ability to comprehend and willingness to comply with the requirements of this protocol, including the QoL questionnaires.
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Female or male patients aged ≥18 years.
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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.
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Life expectancy ≥16 weeks.
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Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
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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.
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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.
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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.
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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.
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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.
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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).
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Combined or mixed hepatocellular/cholangiocarcinoma.
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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.
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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).
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Symptomatic central nervous system or leptomeningeal metastases.
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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.
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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.
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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.
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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.
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Prior exposure to another investigational agent within 28 days prior to randomization.
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Major surgery within 28 days prior to randomization; patient must have completely recovered from any prior surgical or other procedures.
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Pregnant or breastfeeding.
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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.
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Concomitant use of drugs at doses known to cause clinically relevant prolongation of QT/QTc interval.
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Administration of a live vaccination within 28 days prior to randomization.
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Ongoing or recent (≤6 months) hepatorenal syndrome.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A - NUC-1031 and cisplatin NUC-1031 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 B - gemcitabine and cisplatin 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 A - NUC-1031 and cisplatin 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 B - gemcitabine and cisplatin Gemcitabine 1000 mg/m\^2 gemcitabine administered in combination with 25 mg/m\^2 cisplatin on Days 1 and 8 of a 21-day cycle
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From the date of randomization until the date of death from any cause, assessed up to 12 months on average 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.
Objective Response Rate (ORR) 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. 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (125)
University of Kansas Medical Center Research Institute, Inc.
🇺🇸Westwood, Kansas, United States
The Research Foundation for The State University of New York
🇺🇸Stony Brook, New York, United States
The Ohio State University James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
The Medical College of Wisconsin, Inc.
🇺🇸Milwaukee, Wisconsin, United States
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Baptist Health Medical Group Oncology, LLC
🇺🇸Miami, Florida, United States
University of Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
Rocky Mountain Cancer Centers, LLP- Aurora
🇺🇸Aurora, Colorado, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Orlando Health, Inc.
🇺🇸Orlando, Florida, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Royal Victoria Regional Health Centre
🇨🇦Barrie, Ontario, Canada
Fakultní nemocnice Olomouc
🇨🇿Olomouc, Czechia
Fiona Stanley Hospital
🇦🇺Murdoch, Western Australia, Australia
Texas Oncology, P.A. - Tyler
🇺🇸Tyler, Texas, United States
St George Hospital
🇦🇺Kogarah, New South Wales, Australia
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
ICO - Site René Gauducheau
🇫🇷Saint Herblain, France
Thomayerova nemocnice
🇨🇿Prague, Czechia
Medizinische Hochschule Hannover
🇩🇪Hanover, Germany
Fakultní nemocnice Brno
🇨🇿Brno, Czechia
Fakultní nemocnice Hradec Králové
🇨🇿Hradec Králové, Czechia
Nemocnice Na Homolce
🇨🇿Prague, Czechia
Centre Georges François Leclerc
🇫🇷Dijon, France
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Baden Wuerttemberg, Germany
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
🇷🇺Moscow, Russian Federation
Centro Ricerche Cliniche di Verona S.r.l
🇮🇹Verona, Italy
CHU de Grenoble - Hôpital Nord
🇫🇷Grenoble, France
Institut Hospitalier Franco-Britannique
🇫🇷Levallois-Perret, France
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Hôpital Cochin
🇫🇷Paris, France
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸L'Hospitalet De Llobregat, Spain
Vivantes Klinikum Neukoelln
🇩🇪Berlin, Germany
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
🇭🇺Szolnok, Hungary
Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
🇭🇺Budapest, Hungary
Universitaetsklinikum Freiburg
🇩🇪Freiburg, Germany
Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz
🇭🇺Miskolc, Hungary
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Ospedale Policlinico San Martino
🇮🇹Genova, Italy
FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin
🇷🇺Moscow, Russian Federation
State Budget Institution of Healthcare "Leningrad Regional Clinical Oncology Dispensary"
🇷🇺Saint Petersburg, Russian Federation
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Dong-A University Hospital
🇰🇷Pusan, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeollanam-do, Korea, Republic of
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitario HM Madrid Sanchinarro
🇪🇸Madrid, Spain
SPb SBIH "City Clinical Oncological Dispensary"
🇷🇺Saint Petersburg, Russian Federation
Medicinskiy gorod
🇷🇺Tyumen, Russian Federation
"VitaMed" LLC
🇷🇺Moscow, Russian Federation
Pavlov First Saint Petersburg State Medical University
🇷🇺Saint Petersburg, Russian Federation
Baskent University Adana Application and Research Center
🇹🇷Adana, Turkey
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
The Christie
🇬🇧Manchester, Greater Manchester, United Kingdom
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Changhua Christian Medical Foundation Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Acibadem Adana Hospital
🇹🇷Adana, Turkey
Akdeniz University Medical Faculty
🇹🇷Antalya, Turkey
Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital
🇹🇷Malatya, Turkey
Inonu University Medical Facility
🇹🇷Malatya, Turkey
Kyiv City Clinical Oncological Center
🇺🇦Kyiv, Ukraine
Treatment-Prevention Institution Volyn Regional Oncological Dispensary
🇺🇦Luts'k, Ukraine
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
CI Chernivtsi RC Oncological Dispensary
🇺🇦Chernivtsi, Ukraine
Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU
🇺🇦Kharkiv, Ukraine
CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection
🇺🇦Kharkiv, Ukraine
The Clatterbridge Cancer Centre
🇬🇧Wirral, United Kingdom
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Arizona Oncology Associates , PC - HOPE
🇺🇸Tucson, Arizona, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Hospital Universitario Clinico San Carlos
🇪🇸Madrid, Spain
IACT Health
🇺🇸Columbus, Georgia, United States
Affiliated Oncologists LLC
🇺🇸Chicago Ridge, Illinois, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Minnesota Oncology Hemtology
🇺🇸Minneapolis, Minnesota, United States
University of Rochester Medical Center - Strong Memorial Hospital
🇺🇸Rochester, New York, United States
Corporal Michael J. Crescenz VA Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Regents of the University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Texas Oncology, P.A. - Austin
🇺🇸Austin, Texas, United States
Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Wenatchee Valley Hospital and Clinics
🇺🇸Wenatchee, Washington, United States
Northwest Cancer Specialists, P.C.-Vancouver
🇺🇸Vancouver, Washington, United States
Newcastle Private Hospital
🇦🇺Newcastle, New South Wales, Australia
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Sunnybrook Research Institute
🇨🇦Toronto, Ontario, Canada
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Debreceni Egyetem
🇭🇺Debrecen, Hungary
Torbay Hospital
🇬🇧Torquay, United Kingdom
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
CHUM Centre de Recherche
🇨🇦Montréal, Quebec, Canada
SMBD Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
China Medical University Hospital
🇨🇳Taichung, Taiwan
Communal Institution Odesa Regional Clinical Hospital
🇺🇦Odesa, Ukraine
Nova Scotia Health Authority
🇨🇦Halifax, Nova Scotia, Canada
Prisma Health Upstate
🇺🇸Greenville, South Carolina, United States
Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
SI "Shalimov's National Institute of Surgery and Transplantation" of NAMSU
🇺🇦Kyiv, Ukraine
RCI Sumy Regional Clinical Oncological Dispensary
🇺🇦Sumy, Ukraine
Henry Ford Medical Group
🇺🇸Detroit, Michigan, United States
MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital
🇨🇳Taipei, Taiwan
Townsville Cancer Centre
🇦🇺Townsville, Queensland, Australia
Warringal Medical Centre
🇦🇺Heidelberg, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Orszagos Onkologiai Intezet
🇭🇺Budapest, Hungary
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Guy's Hospital
🇬🇧London, Greater London, United Kingdom