A Study of NUC-3373 in Combination With Other Agents in Patients With Colorectal Cancer
NCT ID: NCT05678257
Last Updated: 2025-09-12
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
180 participants
INTERVENTIONAL
2023-04-18
2024-08-29
Brief Summary
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A total of 171 patients will be randomized 1:1:1 to either NUFIRI-bev on a weekly NUC-3373 schedule, NUFIRI-bev based on an alternate weekly NUC-3373 schedule, or FOLFIRI bev on an alternate weekly schedule. The main objectives are to assess and compare the efficacy and safety of the 3 regimens. Pharmacokinetics will be assessed on the 2 NUFIRI arms.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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NUFIRI-bev on a Q1W NUC-3373 schedule
Arm A: Study treatment will be administered in 28-day cycles as follows:
1. Bevacizumab 5 mg/kg on Days 1 and 15:
* 90 minutes for the first dose
* 60 minutes for the second dose (if first dose is tolerated)
* 30 minutes for subsequent doses (if second dose is tolerated)
2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1, 8, 15, and 22.
3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15.
4. NUC-3373 1500 mg/m2 over 120 minutes on Days 1, 8, 15, and 22.
Fosifloxuridine Nafalbenamide
Intravenous infusion
Leucovorin
Intravenous infusion
Irinotecan
Intravenous infusion
Bevacizumab
Intravenous infusion
NUFIRI-bev on a Q2W NUC-3373 schedule
Arm B: Study treatment will be administered in 28-day cycles as follows:
1. Bevacizumab 5 mg/kg on Days 1 and 15:
* 90 minutes for the first dose
* 60 minutes for the second dose (if first dose is tolerated)
* 30 minutes for subsequent doses (if second dose is tolerated)
2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1 and 15.
3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15.
4. NUC-3373 1500 mg/m2 over 120 minutes on Days 1 and 15.
Fosifloxuridine Nafalbenamide
Intravenous infusion
Leucovorin
Intravenous infusion
Irinotecan
Intravenous infusion
Bevacizumab
Intravenous infusion
FOLFIRI-bev on a Q2W schedule
Arm C: Study treatment will be administered in 28-day cycles as follows:
1. Bevacizumab 5 mg/kg on Days 1 and 15:
* 90 minutes for the first dose
* 60 minutes for the second dose (if first dose is tolerated)
* 30 minutes for subsequent doses (if second dose is tolerated)
2. LV 400 mg/m2 (or equivalent levo-LV) over 120 minutes on Days 1 and 15.
3. Irinotecan 180 mg/m2 over 90 minutes (concurrently with the LV infusion) on Days 1 and 15.
4. 5-FU 400 mg/m2 bolus on Days 1 and 15.
5. 5-FU 2400 mg/m2 infusion over 46 hours on Days 1 and 15.
Leucovorin
Intravenous infusion
Irinotecan
Intravenous infusion
Bevacizumab
Intravenous infusion
5-FU
Intravenous infusion
Interventions
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Fosifloxuridine Nafalbenamide
Intravenous infusion
Leucovorin
Intravenous infusion
Irinotecan
Intravenous infusion
Bevacizumab
Intravenous infusion
5-FU
Intravenous infusion
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Histological or cytological confirmation of colorectal adenocarcinoma (excluding appendiceal and anal canal cancers, as well as signet-ring cell carcinoma) that is unresectable and metastatic.
3. Measurable disease (as defined by RECIST v1.1).
4. Received ≥2 months of a first-line fluoropyrimidine and oxaliplatin-containing regimen for metastatic disease or relapsed within 6 months of completing a fluoropyrimidine and oxaliplatin-containing neoadjuvant/adjuvant therapy. Previous treatment with standard of care chemotherapy regimens in combination with molecular targeted therapies (e.g., VEGF and EGFR pathway inhibitors and immuno-oncology agents) is permitted. Previous treatment with maintenance therapy (e.g., capecitabine) is also allowed. Patients who started on a fluoropyrimidine and oxaliplatin-containing regimen in any setting but must discontinue the oxaliplatin due to.toxicity or allergy (and are now unable to receive oxaliplatin) are considered eligible regardless of the number of cycles of oxaliplatin they received.
5. Known RAS and BRAF status. Patients with wild-type RAS tumours must have received prior treatment with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations.
6. Known UGT1A1 status, or patient consents to UGT1A1 status testing if unknown.
7. Known DPD activity status, or patient consents to DPD status testing if unknown. See exclusion criterion 1.
8. Age ≥18 years.
9. Minimum life expectancy of ≥12 weeks.
10. Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
11. Adequate bone marrow function as defined by: absolute neutrophil count (ANC) ≥1.5 × 109/L, platelet count ≥100 × 109/L, and haemoglobin ≥9 g/dL. Patients with benign neutropenia may be discussed on a case-by-case basis with the medical monitor.
12. Adequate liver function, as defined by: serum total bilirubin ≤1.5 × ULN), AST and ALT ≤2.5 × ULN (or ≤5 × ULN if liver metastases are present).
13. Adequate renal function assessed as serum creatinine \<1.5 × ULN and glomerular filtration rate ≥50 mL/min (calculated by the Cockcroft-Gault method).
14. Serum albumin ≥3 g/dL.
15. Ability to comply with protocol requirements.
16. Female patients of child-bearing potential must have a negative serum pregnancy test within 7 days prior to the first study drug administration. This criterion does not apply to patients who have had a previous hysterectomy or bilateral oophorectomy. Male patients and female patients of child-bearing potential must agree to practice true abstinence (defined in Section 10.3.1) or to use two forms of contraception, one of which must be highly effective. These forms of contraception must be used from the time of signing consent, throughout the treatment period, and for 6 months following the last dose of any study medication. Oral or injectable contraceptive agents cannot be the sole method of contraception
17. Patients must have been advised to take measures to avoid or minimize exposure of the skin and eyes to UV light, including avoiding sunbathing and solarium use, for the duration of study participation and for a period of 4 weeks following the last dose of study medication
Exclusion Criteria
2. History of hypersensitivity or current contra-indication to any of the combination agents required for the study.
3. History of allergic reactions attributed to components of the NUC-3373 drug product formulation.
4. History of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies.
5. History of or known central nervous system or leptomeningeal metastases.
6. Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months.
7. Mutant BRAF V600E status.
8. MSI high or dMMR.
9. Prior treatment with irinotecan.
10. Chemotherapy, hormonal therapy, radiotherapy (other than a short cycle of palliative radiotherapy \[e.g., for bone pain\]\*), immunotherapy, biological agents, or exposure to another investigational agent within 21 days (or four times the half-life for molecular targeted agents, whichever is shorter) of first administration of study treatment:
11. Residual toxicities from prior chemotherapy or radiotherapy which have not regressed to Grade ≤1 severity (CTCAE v5.0), except for alopecia and residual Grade 2 neuropathy.
12. 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. Patients with previous invasive cancers are eligible if treatment was completed \>3 years prior to initiating the current study treatment, and the patient has had no evidence or recurrence since then.
13. Presence of an active bacterial or viral infection (including SARS-CoV-2, Herpes Zoster, Varicella Zoster or chickenpox), known Human Immunodeficiency Virus (HIV) positive or known active hepatitis B or C.
14. Presence of any uncontrolled concurrent serious illness, medical condition or other medical history, including laboratory results, which, in the Investigator's opinion, would be likely to interfere with the patient's ability to participate in the study or with the interpretation of the results (refer to protocol for further details).
15. Any condition that, in the judgment of the Investigator, may affect the patient's ability to provide informed consent and undergo study procedures.
16. Patients with a history of haemoptysis (1/2 teaspoon or more of red blood) within 6 months prior to enrolment.
17. Wound healing complications or surgery within 28 days of starting bevacizumab (wound healing must have been fully completed before starting bevacizumab). Investigators may allow patients to initiate treatment with the other study drugs (i.e., NUC-3373/5-FU, LV and irinotecan) on C1D1 but withhold bevacizumab for at least 15 days, but no longer than 28 days, to allow completion of wound healing in patients who would otherwise be eligible for the study, in line with standard local practice and after discussion with the Medical Monitor. Patients who have not received bevacizumab by C2D1 must be replaced.
18. Unhealed wound, active gastric or duodenal ulcer, or bone fracture.
19. Serious thromboembolic event in the 6 months before inclusion.
20. Patients with a history of haemorrhage within 6 months prior to enrolment.
21. Known inherited or acquired bleeding disorders.
22. Red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening.
23. Uncontrolled hypertension.
24. Severe proteinuria or nephrotic syndrome.
25. Acute intestinal obstruction or sub-obstruction, history of inflammatory intestinal disease or extended resection of the small intestine. Presence of a colic prosthesis.
26. History of abdominal fistulas, trachea-oesophageal fistulas, any other Grade 4 gastrointestinal perforations, non-gastrointestinal fistulas, or intra-abdominal abscesses 6 months prior to screening.
27. Currently pregnant, lactating or breastfeeding.
28. Required concomitant use of brivudine, sorivudine and analogues.
29. Required concomitant use of St John's Wort.
30. Required concomitant use of drugs known to prolong QT/QTc interval.
31. Required concomitant use of strong CYP3A4 inducers or strong CYP3A4 inhibitors. The use of strong CYP3A4 inducers within 2 weeks of first receipt of study drug or the use of strong CYP3A4 inhibitors within 1 week of first receipt of study drug is also excluded.
18 Years
ALL
No
Sponsors
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NuCana plc
OTHER
Responsible Party
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Principal Investigators
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Elisabeth Oelmann, MD, PhD
Role: STUDY_DIRECTOR
NuCana plc
Locations
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Helen F. Graham Cancer Center
Newark, Delaware, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
University of Florida Health Medical Oncology - Davis Cancer Pavilion
Gainesville, Florida, United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Cancer Center of Kansas
Wichita, Kansas, United States
Norton Cancer Institute
Louisville, Kentucky, United States
Boston Medical Center
Boston, Massachusetts, United States
University of Massachusetts Worcester
Worcester, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States
Morristown Medical Center
Morristown, New Jersey, United States
The Christ Hospital Cancer Center
Cincinnati, Ohio, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
USOR - Texas Oncology Northeast Texas
Tyler, Texas, United States
Fred Hutchinson Cancer Center at Evergreen Health
Kirkland, Washington, United States
Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center
Vancouver, Washington, United States
Strasbourg Oncology Liberale - Clinique Sainte-Anne
Strasbourg, Alsace, France
Hôpital Européen Marseille
Marseille, Bouches-du-Rhône, France
Centre Georges-François Leclerc
Dijon, Bourgogne-Franche-Comté, France
Centre Hospitalier Régional et Universitaire de Besançon - Hôpital Jean-Minjoz
Besançon, Doubs, France
Institut Bergonié
Bordeaux, Gironde, France
Centre Hospitalier Universitaire de Poitiers
Poitiers, Vienne, France
Centre Hospitalier UniversitaireNantes - Hôtel Dieu
Nantes, , France
Hôpital Européen Georges-Pompidou
Paris, Île-de-France Region, France
Hôpital Foch
Suresnes, Île-de-France Region, France
München Klinik Neuperlach
München, Bavaria, Germany
Krankenhaus Nordwest
Frankfurt am Main, Hesse, Germany
Universitätsklinik Ulm - Oberen Eselsberg
Ulm, Tübingen, Germany
Charité Campus Virchow-Klinikum
Berlin, , Germany
Azienda Ospedaliera Universitaria - Università degli Studi della Campania Luigi Vanvitelli
Napoli, Campania, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Lombardy, Italy
Ospedale Santa Maria delle Croci di Ravenna
Faenza, Ravenna, Italy
Azienda Ospedaliero Universitaria Careggi
Florence, Tuscany, Italy
Istituto Oncologico Veneto - IRCCS
Padua, Veneto, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona
Ancona, , Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, , Italy
Azienda Ospedaliera Regionale San Carlo
Potenza, , Italy
Institut Català d'Oncologia - ICO Badalona - Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, Spain
Complejo Hospitalario Universitario de Santiago (CHUS)
Santiago de Compostela, La Coruña, Spain
Hospital Universitario Fundación Alcorcón
Alcorcón, Madrid, Spain
Hospital Universitario Puerta de Hierro
Majadahonda, Madrid, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, , Spain
Hospital Universitari Vall d'Hebrón
Barcelona, , Spain
Hospital Duran i Reynals
Barcelona, , Spain
Hospital de León
León, , Spain
Hospital Universitari Arnau de Vilanova
Lleida, , Spain
Hospital General Universitario Gregorio Marañón
Madrid, , Spain
MD Anderson Cancer Center Madrid
Madrid, , Spain
Hospital Universitario 12 de Octubre
Madrid, , Spain
Hospital Universitario Virgen de la Victoria
Málaga, , Spain
Hospital Universitario Virgen del Rocío
Seville, , Spain
Queen's Hospital
Romford, Essex, United Kingdom
University College London Hospitals NHS Foundation Trust
London, Greater London, United Kingdom
Royal Free London NHS Foundation Trust
London, Greater London, United Kingdom
Guy's and Saint Thomas' NHS Foundation Trust
London, Greater London, United Kingdom
The Christie NHS Foundation Trust
Manchester, Lancashire, United Kingdom
Mount Vernon Cancer Centre - East and North Hertfordshire NHS Trust
Northwood, Middlesex, United Kingdom
Velindre University NHS Trust
Cardiff, , United Kingdom
NHS Greater Glasgow and Clyde
Glasgow, , United Kingdom
Countries
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Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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2022-001459-17
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NuTide:323
Identifier Type: -
Identifier Source: org_study_id
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