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

Biliary Tract Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04163900
• Other study ID #: NuTide:121
• Secondary ID: 2019-001025-28
• Status: Terminated
• Phase: Phase 3
• Start date: December 24, 2019
• Est. completion date: April 5, 2022

Study information

• Verified date: May 2023
• Source: NuCana plc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 773
• Est. completion date: April 5, 2022
• Est. primary completion date: March 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms

Intervention

Drug:
• NUC-1031
IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes
• Gemcitabine
IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert
• Cisplatin
IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Warringal Medical Centre	Heidelberg	Victoria
Australia	St George Hospital	Kogarah	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Newcastle Private Hospital	Newcastle	New South Wales
Australia	Townsville Cancer Centre	Townsville	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	CHUM Centre de Recherche	Montréal	Quebec
Canada	SMBD Jewish General Hospital	Montréal	Quebec
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Czechia	Fakultní nemocnice Brno	Brno
Czechia	Fakultní nemocnice Hradec Králové	Hradec Králové
Czechia	Fakultní nemocnice Olomouc	Olomouc
Czechia	Nemocnice Na Homolce	Prague
Czechia	Thomayerova nemocnice	Prague
France	Centre Georges François Leclerc	Dijon
France	CHU de Grenoble - Hôpital Nord	Grenoble
France	Institut Hospitalier Franco-Britannique	Levallois-Perret
France	Hôpital Cochin	Paris
France	ICO - Site René Gauducheau	Saint Herblain
Germany	Vivantes Klinikum Neukoelln	Berlin
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Medizinische Hochschule Hannover	Hanover
Germany	Universitaetsklinikum Heidelberg	Heidelberg	Baden Wuerttemberg
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Orszagos Onkologiai Intezet	Budapest
Hungary	Semmelweis Egyetem	Budapest
Hungary	Debreceni Egyetem	Debrecen
Hungary	Borsod-Abauj-Zemplen Megyei Kozponti Korhaz es Egyetemi Oktatokorhaz	Miskolc
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet	Szolnok
Italy	Ospedale Policlinico San Martino	Genova
Italy	IEO Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	IOV - Istituto Oncologico Veneto IRCCS	Padova
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Centro Ricerche Cliniche di Verona S.r.l	Verona
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun	Jeollanam-do
Korea, Republic of	Dong-A University Hospital	Pusan
Korea, Republic of	CHA Bundang Medical Center, CHA University	Seongnam-si	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University	Seoul
Russian Federation	"VitaMed" LLC	Moscow
Russian Federation	FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"	Moscow
Russian Federation	FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin	Moscow
Russian Federation	Pavlov First Saint Petersburg State Medical University	Saint Petersburg
Russian Federation	SPb SBIH "City Clinical Oncological Dispensary"	Saint Petersburg
Russian Federation	State Budget Institution of Healthcare "Leningrad Regional Clinical Oncology Dispensary"	Saint Petersburg
Russian Federation	Medicinskiy gorod	Tyumen
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	ICO l'Hospitalet - Hospital Duran i Reynals	L'Hospitalet De Llobregat
Spain	Hospital General Universitario Gregorio Marañon	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Universitario HM Madrid Sanchinarro	Madrid
Spain	Hospital Universitario Virgen del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
Taiwan	Changhua Christian Medical Foundation Changhua Christian Hospital	Changhua
Taiwan	China Medical University Hospital	Taichung
Taiwan	MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Turkey	Acibadem Adana Hospital	Adana
Turkey	Baskent University Adana Application and Research Center	Adana
Turkey	Akdeniz University Medical Faculty	Antalya
Turkey	Trakya University Medical Faculty	Edirne
Turkey	Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty	Istanbul
Turkey	Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital	Malatya
Turkey	Inonu University Medical Facility	Malatya
Ukraine	CI Chernivtsi RC Oncological Dispensary	Chernivtsi
Ukraine	CI of Healthcare Regional Clinical Specialized Dispensary of the Radiation Protection	Kharkiv
Ukraine	Communal Non-profit Enterprise Regional Center of Oncology, Kharkiv NMU	Kharkiv
Ukraine	Kyiv City Clinical Oncological Center	Kyiv
Ukraine	SI "Shalimov's National Institute of Surgery and Transplantation" of NAMSU	Kyiv
Ukraine	Treatment-Prevention Institution Volyn Regional Oncological Dispensary	Luts'k
Ukraine	Communal Institution Odesa Regional Clinical Hospital	Odesa
Ukraine	RCI Sumy Regional Clinical Oncological Dispensary	Sumy
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Guy's Hospital	London	Greater London
United Kingdom	The Christie	Manchester	Greater Manchester
United Kingdom	Torbay Hospital	Torquay
United Kingdom	The Clatterbridge Cancer Centre	Wirral
United States	Rocky Mountain Cancer Centers, LLP- Aurora	Aurora	Colorado
United States	Texas Oncology, P.A. - Austin	Austin	Texas
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Affiliated Oncologists LLC	Chicago Ridge	Illinois
United States	IACT Health	Columbus	Georgia
United States	The Ohio State University James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Henry Ford Medical Group	Detroit	Michigan
United States	Prisma Health Upstate	Greenville	South Carolina
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Baptist Health Medical Group Oncology, LLC	Miami	Florida
United States	The Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Minnesota Oncology Hemtology	Minneapolis	Minnesota
United States	Regents of the University of Minnesota	Minneapolis	Minnesota
United States	Orlando Health, Inc.	Orlando	Florida
United States	Corporal Michael J. Crescenz VA Medical Center	Philadelphia	Pennsylvania
United States	University of Rochester Medical Center - Strong Memorial Hospital	Rochester	New York
United States	Virginia Mason Medical Center	Seattle	Washington
United States	The Research Foundation for The State University of New York	Stony Brook	New York
United States	Arizona Oncology Associates , PC - HOPE	Tucson	Arizona
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology, P.A. - Tyler	Tyler	Texas
United States	Northwest Cancer Specialists, P.C.-Vancouver	Vancouver	Washington
United States	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington
United States	University of Kansas Medical Center Research Institute, Inc.	Westwood	Kansas
United States	The Oncology Institute of Hope and Innovation	Whittier	California
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
NuCana plc

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Russian Federation,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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