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

NCT ID: NCT04163900

Last Updated: 2023-05-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 773 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-24
• Study Completion Date: 2022-04-05

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

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

Group Type: EXPERIMENTAL

NUC-1031

Intervention Type: DRUG

IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes

Cisplatin

Intervention Type: DRUG

IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

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

Group Type: ACTIVE_COMPARATOR

Gemcitabine

Intervention Type: DRUG

IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert

Cisplatin

Intervention Type: DRUG

IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

Interventions

NUC-1031

IV infusion in 500 mL of 0.9% sterile saline for injection given over 30 minutes

Intervention Type: DRUG

Gemcitabine

IV infusion in 250 mL of 0.9% sterile saline for injection given in accordance with the package insert

Intervention Type: DRUG

Cisplatin

IV in accordance with local institutional practice for biliary tract cancer, including the use of an appropriate hydration protocol

Intervention Type: DRUG

Other Intervention Names

fosgemcitabine palabenamide; Difluorodeoxycytidine; Gemzar; CDDP

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NuCana plc

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer Knox, MD

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine, University of Toronto

Locations

Dong-A University Hospital

Pusan, , South Korea

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital de la Santa Creu i Sant Pau

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 Macarena

Seville, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Changhua Christian Medical Foundation Changhua Christian Hospital

Changhua, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

MacKay Medical Foundation The Presbyterian Church in Taiwan MacKay Memorial Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Acibadem Adana Hospital

Adana, , Turkey (Türkiye)

Baskent University Adana Application and Research Center

Adana, , Turkey (Türkiye)

Akdeniz University Medical Faculty

Antalya, , Turkey (Türkiye)

Trakya University Medical Faculty

Edirne, , Turkey (Türkiye)

Istanbul University Cerrahpasa - Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Dr. Abdurrahman Yurtaslan Oncology Teaching and Research Hospital

Malatya, , Turkey (Türkiye)

Inonu University Medical Facility

Malatya, , Turkey (Türkiye)

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

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

Lutsk, , Ukraine

Communal Institution Odesa Regional Clinical Hospital

Odesa, , Ukraine

RCI Sumy Regional Clinical Oncological Dispensary

Sumy, , Ukraine

Guy's Hospital

London, Greater London, United Kingdom

The Christie

Manchester, Greater Manchester, United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

The Clatterbridge Cancer Centre

Metropolitan Borough of Wirral, , United Kingdom

Torbay Hospital

Torquay, , United Kingdom

Arizona Oncology Associates , PC - HOPE

Tucson, Arizona, United States

University of Arizona Cancer Center

Tucson, Arizona, United States

The Oncology Institute of Hope and Innovation

Whittier, California, United States

Rocky Mountain Cancer Centers, LLP- Aurora

Aurora, Colorado, United States

Baptist Health Medical Group Oncology, LLC

Miami, Florida, United States

Orlando Health, Inc.

Orlando, Florida, United States

IACT Health

Columbus, Georgia, United States

Affiliated Oncologists LLC

Chicago Ridge, Illinois, United States

University of Kansas Medical Center Research Institute, Inc.

Westwood, Kansas, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Henry Ford Medical Group

Detroit, Michigan, United States

Minnesota Oncology Hemtology

Minneapolis, Minnesota, United States

Regents of the University of Minnesota

Minneapolis, Minnesota, United States

University of Rochester Medical Center - Strong Memorial Hospital

Rochester, New York, United States

The Research Foundation for The State University of New York

Stony Brook, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

The Ohio State University James Cancer Hospital and Solove Research Institute

Columbus, Ohio, United States

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, Pennsylvania, United States

Prisma Health Upstate

Greenville, South Carolina, 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

Texas Oncology, P.A. - Tyler

Tyler, Texas, United States

Virginia Mason Medical Center

Seattle, Washington, United States

Northwest Cancer Specialists, P.C.-Vancouver

Vancouver, Washington, United States

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, United States

The Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, United States

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

St George Hospital

Kogarah, New South Wales, Australia

Newcastle Private Hospital

Newcastle, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Townsville Cancer Centre

Townsville, Queensland, Australia

Warringal Medical Centre

Heidelberg, Victoria, Australia

The Alfred Hospital

Melbourne, Victoria, Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Nova Scotia Health Authority

Halifax, Nova Scotia, Canada

Royal Victoria Regional Health Centre

Barrie, Ontario, Canada

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada

Sunnybrook Research Institute

Toronto, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

CHUM Centre de Recherche

Montreal, Quebec, Canada

SMBD Jewish General Hospital

Montreal, Quebec, Canada

Fakultní nemocnice Brno

Brno, , Czechia

Fakultní nemocnice Hradec Králové

Hradec Králové, , Czechia

Fakultní nemocnice Olomouc

Olomouc, , Czechia

Thomayerova nemocnice

Prague, , Czechia

Nemocnice Na Homolce

Prague, , Czechia

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, , France

Universitaetsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Vivantes Klinikum Neukoelln

Berlin, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Semmelweis Egyetem

Budapest, , Hungary

Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet

Budapest, , Hungary

Orszagos Onkologiai Intezet

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, , Hungary

Ospedale Policlinico San Martino

Genova, , Italy

IEO Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, , Italy

IOV - Istituto Oncologico Veneto IRCCS

Padua, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Centro Ricerche Cliniche di Verona S.r.l

Verona, , Italy

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, , Russia

FSBSI Russian Oncological Scientific Center n.a. N.N. Blokhin

Moscow, , Russia

"VitaMed" LLC

Moscow, , Russia

State Budget Institution of Healthcare "Leningrad Regional Clinical Oncology Dispensary"

Saint Petersburg, , Russia

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

SPb SBIH "City Clinical Oncological Dispensary"

Saint Petersburg, , Russia

Medicinskiy gorod

Tyumen, , Russia

CHA Bundang Medical Center, CHA University

Seongnam-si, Gyeonggi-do, South Korea

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Countries

United States; Australia; Canada; Czechia; France; Germany; Hungary; Italy; Russia; South Korea; Spain; Taiwan; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39978598 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32374623 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-001025-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NuTide:121

Identifier Type: -

Identifier Source: org_study_id