Colorectal CancerPhase 1/2NCT03428958

A Safety, Pharmacokinetic and Efficacy Study of NUC-3373 in Combination With Standard Agents Used in Colorectal Cancer Treatment

A Phase 1/2 study testing NUC-3373 + leucovorin, NUC-3373 and NUFOX in people with Colorectal Cancer and Colorectal Neoplasms, run by NuCana plc at 10 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a three-part study of NUC-3373 administered by intravenous (IV) infusion across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat CRC (leucovorin, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Cancer, Colorectal Neoplasms, Colorectal Carcinoma
What is being tested?: NUC-3373 + leucovorin, NUC-3373 and NUFOX
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 111 participants
Where: 10 sitesin 3 countries
Study dates: 5 Oct 2018to 21 Mar 2024
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

All patients
Provision of written informed consent
Have histological confirmation of CRC with evidence of locally advanced/unresectable or metastatic disease
Age ≥18 years
Life expectancy of ≥12 weeks
ECOG Performance status 0 or 1

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Measurable disease as defined by RECIST v1.1
Known RAS and BRAF status. Patients with wild-type KRAS tumours who are to be enrolled to a cohort that does not contain an EGFR pathway inhibitor (Arms 2a, 2b, 2c, 2d, 3a, 3b, 3c, 3d and 3e) must have received prior treatment with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations. Patients with BRAF V600E mutant tumours should have received prior treatment with encorafenib in combination with an EGFR inhibitor, unless this was not standard of care according to relevant region-specific treatment recommendations
Adequate bone marrow function as defined by: ANC ≥1.5×10^9/L, platelet count ≥100×10^9/L (with no evidence of bleeding), and haemoglobin ≥9 g/dL
Adequate liver function as defined by serum total bilirubin ≤1.5×ULN, AST and ALT ≤2.5×ULN (or ≤5×ULN if liver metastases present)
Adequate renal function assessed as serum creatinine <1.5×ULN or glomerular filtration rate ≥50 mL/min. This criterion does not apply to Arm 1d.
Serum albumin ≥3 g/dL
For the cohort in which the patient will participate, there are no contra-indications to receiving the approved partner combination drugs
Ability to comply with protocol requirements
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 or to use two highly effective forms of contraception, one of which must be a barrier method.
Patients must have been advised to take measures to avoid or minimise exposure to UV light for the duration of study participation and for a period of 4 weeks following the last dose of study medication
Male patients receiving oxaliplatin must have been offered advice on and/or sought counselling for conservation of sperm prior to the first dose of study medication
>3rd-line patients
Received at least two prior lines of therapy for locally advanced or metastatic CRC, including one fluoropyrimidine plus oxaliplatin and one fluoropyrimidine plus irinotecan containing regimen. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received FOLFOXIRI-based regimens in 1st-/2nd-line settings may be included.
Patients due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
Patients due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based therapy
2nd-/3rd-line patients
Received at least one but no more than two prior lines of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic CRC. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received FOLFOXIRI-based regimens in 1st-/2nd-line settings may be included. 3rd-line patients enrolled to Arms 2c and 2d must have received prior bevacizumab treatment, unless ineligible or unless bevacizumab was not standard of care according to relevant region-specific treatment recommendations
Patients in Part 2 due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
Patients in Part 2 due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based regimen
Combination chemotherapy ineligible patients
May have received one prior fluoropyrimidine-containing regimen for locally advanced or metastatic CRC
Ineligible to receive combination therapy for locally advanced or metastatic CRC
Creatinine clearance >30mL/min
Rapid progressors
Received no more than two prior lines of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic CRC. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received FOLFOXIRI-based regimens in 1st-/2nd-line settings may be included.
Have had tumour progression ≤3 months of starting the last fluoropyrimidine-containing regimen
Patients due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
Patients due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based regimen
2nd-line patients
1. Received one prior line of fluoropyrimidine-containing therapy in combination with oxaliplatin and/or irinotecan for locally advanced or metastatic CRC. Previous treatment with SoC regimens in combination with molecular targeted therapies is permitted and patients who received triplet chemotherapy based regimens is allowed.
Maintenance patients
Received at least 12 weeks of 1st-line SoC therapy for locally advanced or metastatic CRC and achieved at least stable disease
Eligible for maintenance therapy

Who cannot join

All patients
Prior history of hypersensitivity or current contra-indications to 5-FU or capecitabine
Prior history of hypersensitivity or current contra-indications to any of the combination agents required for the study arm to which the patient is assigned
History of allergic reactions attributed to the components of the NUC-3373 drug product formulation
Symptomatic CNS or leptomeningeal metastases
Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months

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Chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy [e.g. for bone pain]), immunotherapy or exposure to another investigational agent within 28 days (or five times half-life for a biological or molecular targeted agent or three times the half-life for an immunotherapy agent) of first receipt of study drug
Residual toxicities from prior chemotherapy or radiotherapy, which have not regressed to Grade ≤1 severity (CTCAE v5.0) except for alopecia. In cohorts not containing oxaliplatin, residual Grade 2 neuropathy is allowed.
History of another malignancy diagnosed within the past 5 years, with the exception of adequately treated non-melanoma skin cancer curatively treated carcinoma in situ 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 there is no evidence of recurrence.
Presence of active bacterial or viral infection (including SARS-CoV-2, Herpes Zoster or chicken pox), known HIV positive or known active hepatitis B or C
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 their participation in the study, or with the interpretation of the results
Any condition (e.g. known or suspected poor compliance, psychological instability, geographical location) that, in the judgment of the Investigator, may affect the patient's ability to sign the informed consent and undergo study procedures
Currently pregnant, lactating or breastfeeding
QTc interval >450 milliseconds for males and >470 milliseconds for females
Required concomitant use of drugs known to prolong QT/QTc interval
Required concomitant use of strong CYP3A4 inducers or strong CYP3A4 inhibitors, or use of strong CYP3A4 inducers within 2 weeks of first receipt of study drug or use of strong CYP3A4 inhibitors within 1 week of first receipt of study drug
For patients receiving irinotecan: Use of strong UGT1A1 inhibitors within 1 week of first receipt of study drug
Has received a live vaccination within four weeks of first planned dose of study medication
Known DPD or TYMP mutations associated with toxicity to fluoropyrimidines
Use of warfarin and other types of long acting anti-coagulants is prohibited within 4 weeks of the first dose of study treatment
Patients receiving bevacizumab
Patients with a history of haemoptysis (≥1/2 tsp of red blood)
Wound healing complications or surgery within 28 days of starting bevacizumab
Severe chronic wounds, ulcers or bone fracture
Arterial thromboembolic events or haemorrhage within 6 months prior to study entry (except for tumour bleeding surgically treated by tumour resection)
Bleeding diatheses or coagulopathy
Receiving full-dose anti-coagulation treatment
Uncontrolled hypertension
Clinically significant coronary heart disease or myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia
Severe proteinuria
Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhoea
Any contraindications present in the bevacizumab Prescribing Information
Patients receiving cetuximab or panitumumab
Clinically significant coronary heart disease or myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia
Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhoea
Hypomagnesaemia or hypokalaemia not controlled by oral therapy
Any contraindications present in the cetuximab or panitumumab Prescribing Information

Trial locations and contacts

10 sites in 3 countries.

Country

City, postcode or hospital

10 sites in 3 countries

United States6 sites

Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Duke University Medical Center
Durham, North Carolina, 27710
Vanderbilt University
Nashville, Tennessee, 37232
Seattle Cancer Center
Seattle, Washington, 98109-1023
Compass Oncology
Vancouver, Washington, 98684

Other trials in United States

United Kingdom3 sites

The Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
University College London Hospitals NHS Foundation Trust
London, W1T 7HA
University of Oxford
Oxford, OX3 7LE

Other trials in United Kingdom

France1 site

Hopital Franco-Britannique
Levallois-Perret, 92300

Other trials in France

About this study

Official title: A Phase Ib/II Open Label Study to Assess the Safety and Pharmacokinetics of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Agents Used in Colorectal Cancer Treatment

Conditions: Colorectal Cancer, Colorectal Neoplasms, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal
Being tested: NUC-3373 + leucovorin, NUC-3373, NUFOX, NUFOX + VEGF pathway inhibitor, NUFOX + EGFR inhibitor
Keywords: Relapsed metastatic adenocarcinoma of colon/rectum
Medical subject headings: Colorectal Neoplasms, Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NUC-3373 + leucovorinDrug
Also called folinic acid, levoleucovorin, Nucleotide analogue
NUC-3373 + leucovorin
NUC-3373Drug
Also called Nucleotide analogue
NUC-3373
NUFOXDrug
Also called Eloxatin, Nucleotide analogue
NUC-3373 + oxaliplatin
NUFOX + VEGF pathway inhibitorDrug
Also called Eloxatin, Avastin, Nucleotide analogue
NUC-3373 + oxaliplatin + bevacizumab
NUFOX + EGFR inhibitorDrug
Also called Eloxatin, Erbitux, Nucleotide analogue, Vectibix
NUC-3373 + oxaliplatin + cetuximab/panitumumab
NUFIRIDrug
Also called Campto, Camptosar, Nucleotide analogue
NUC-3373 + irinotecan
NUFIRI + VEGF pathway inhibitorDrug
Also called Campto, Camptosar, Avastin, Nucleotide analogue
NUC-3373 + irinotecan + bevacizumab
NUFIRI + EGFR inhibitorDrug
Also called Campto, Camptosar, Erbitux, Nucleotide analogue
NUC-3373 + irinotecan + cetuximab/panitumumab
NUC-3373 + bevacizumabDrug
Also called Nucleotide analogue, Avastin
NUC-3373 + bevacizumab

Study groups in NCT03428958
Study group	Role	What they receive
NUC-3373 + leucovorin (LV) every other week	Experimental	Arm 1a: NUC-3373 administered IV followed by a 2-week washout period. The next dose of NUC-3373 administered in combination with LV at 400 mg/m2. All subsequent doses of NUC-3373 administered in combination with LV every 2 weeks in 28-day cycles. Receives: Drug: NUC-3373 + leucovorin
NUC-3373 every other week	Experimental	Arm 1b: LV 400 mg/m2 administered IV over 2 hours prior to NUC-3373 infusion followed by a 2-week washout period. Then, NUC-3373 administered IV every 2 weeks without LV in 28-day cycles. Receives: Drug: NUC-3373
NUC-3373 + leucovorin (LV) weekly	Experimental	Arm 1c: LV 400 mg/m2 administered IV over 2 hours followed by NUC-3373 administered IV weekly on Days 1, 8, 15 and 22 of 28-day cycles. Receives: Drug: NUC-3373 + leucovorin
NUC-3373 + leucovorin (LV); combination chemotherapy ineligible	Experimental	Arm 1d: LV 400 mg/m2 administered IV over 2 hours followed by NUC-3373 administered IV on Days 1, 8, 15 and 22 of 28-day cycles. Receives: Drug: NUC-3373 + leucovorin
NUC-3373 + oxaliplatin weekly	Experimental	Arm 2a: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with oxaliplatin (85 mg/m2) administered on Days 1 and 15. Receives: Drug: NUFOX
NUC-3373 + irinotecan weekly	Experimental	Arm 2b: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with irinotecan (180 mg/m2) on Days 1 and 15. Receives: Drug: NUFIRI
NUC-3373 + oxaliplatin (NUFOX) expansion	Experimental	Arm 2c: At the completion of Arm 2a, the recommended dose of NUC-3373 (+LV 400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with oxaliplatin (85 mg/m2) administered on Days 1 and 15. Receives: Drug: NUFOX
NUC-3373 + irinotecan (NUFIRI) expansion	Experimental	Arm 2d: At the completion of Arm 2b, the recommended dose of NUC-3373 (+LV 400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with irinotecan (180 mg/m2) on Days 1 and 15. Receives: Drug: NUFIRI
NUFOX + bevacizumab weekly	Experimental	Arm 3a: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a will be combined with bevacizumab. NUC-3373+LV will be administered weekly, oxaliplatin and bevacizumab will be administered every other week. Receives: Drug: NUFOX + VEGF pathway inhibitor
NUFOX + bevacizumab every other week	Experimental	Arm 3b: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a will be combined with bevacizumab. NUC-3373+LV+oxaliplatin+bevacizumab will be administered every other week. Receives: Drug: NUFOX + VEGF pathway inhibitor
NUFIRI + bevacizumab weekly	Experimental	Arm 3c: NUC-3373, LV and irinotecan at dose levels used in Arm 2b will be combined with bevacizumab. NUC-3373+LV will be administered weekly, irinotecan and bevacizumab will be administered every other week. Receives: Drug: NUFIRI + VEGF pathway inhibitor
NUFIRI + bevacizumab every other week	Experimental	Arm 3d: NUC-3373, LV and irinotecan at dose levels used in Arm 2b will be combined with bevacizumab. NUC-3373+LV+irinotecan+bevacizumab will be administered every other week. Receives: Drug: NUFIRI + VEGF pathway inhibitor
NUC-3373 + LV + bevacizumab; maintenance patients	Experimental	Arm 3e: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with bevacizumab (administered every other week). Receives: Drug: NUC-3373 + bevacizumab
NUFOX + cetuximab	Experimental	Arm 3f: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a may be administered in subsequent cetuximab cohorts. NUC-3373+LV may be administered weekly or every other week, oxaliplatin will be administered every other week and cetuximab will be administered weekly. Receives: Drug: NUFOX + EGFR inhibitor
NUFIRI + cetuximab	Experimental	Arm 3g: NUC-3373, LV and irinotecan at dose levels used in Arm 2b may be administered in subsequent cetuximab cohorts. NUC-3373+LV may be administered weekly or every other week, irinotecan will be administered every other week and cetuximab will be administered weekly. Receives: Drug: NUFIRI + EGFR inhibitor

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage Change From Baseline in Tumour Size
Efficacy (per RECIST v 1.1): defined as the best percentage change from baseline in tumour size (mm)
Measured: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Disease Control Rate (DCR)
Efficacy (per RECIST v 1.1): defined as the proportion of patients achieving confirmed response (CR and PR) or stable disease (SD) as the best overall response
Measured: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Duration of Stable Disease (DoSD)
Efficacy (per RECIST v 1.1): defined as the time from the time measurement criteria are first met for SD until the first date that recurrence or progressive disease (PD) is objectively documented
Measured: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Progression Free Survival (PFS)
Efficacy (per RECIST v 1.1): defined as the time from first dose of study treatment until the date of objective disease progression or death
Measured: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Overall Survival (OS)
Efficacy: defined as the time from randomization until the date of death from any cause
Measured: From the date of randomization until the date of death from any cause, until the end of study (up to 25 months)]
Best Overall Response
Best overall response to study treatment according to RECIST v1.1
Measured: Assessed every 8 weeks from Day 1 until the end of study (up to 25 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Oct 201821 Mar 2024

First posted12 Feb 2018
Study start5 Oct 2018
Primary completion19 Mar 2024
Study completion21 Mar 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Colorectal CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: This is a three-part study of NUC-3373 administered by IV across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat CRC (LV, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). Part 1 will determine if NUC-3373 should be administered with LV. Part 2 consists of a dose escalation phase, to assess the safety/tolerability of different doses of NUC-3373 in combination with either oxaliplatin (NUFOX) or irinotecan (NUFIRI), and an expansion phase, to assess weekly schedules of NUFOX and NUFIRI regimens selected in the escalation phase. Part 3 will assess the safety/efficacy of NUFOX and NUFIRI regimens administered in combination with bevacizumab, cetuximab or panitumumab. Additional patients may be enrolled in all parts to replace patients who withdraw prior to completing the 28-day safety evaluation period to complete the min number patients per cohort. Enrolment may be expanded at the DSMCs discretion.
Masking: None (open label)
Enrolment: 111 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03428958
Sponsor's protocol ID: NuTide:302
Other IDs: 2017-002062-53, 2017
Status last verified: Mar 2025
First submitted: 2 Feb 2018
Last updated: 23 Apr 2025
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 23 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase Ib/II Open Label Study to Assess the Safety and Pharmacokinetics of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Agents Used in Colorectal Cancer Treatment
ClinicalTrials.gov ID: NCT03428958
Acronym / sponsor ID: NuTide:302
Conditions: Colorectal Cancer, Colorectal Neoplasms, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal
Keywords: Relapsed metastatic adenocarcinoma of colon/rectum
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 111 participants (actual)
Lead sponsor: NuCana plcUniversity, hospital or other
Study start: 5 Oct 2018 (actual)
Primary completion: 19 Mar 2024 (actual)
Study completion: 21 Mar 2024 (actual)
First posted: 12 Feb 2018 (actual)
Results: Posted 23 Apr 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 15
Model description: This is a three-part study of NUC-3373 administered by IV across two administration schedules, either as monotherapy or as part of various combinations with agents commonly used to treat CRC (LV, oxaliplatin, irinotecan, bevacizumab, cetuximab and panitumumab). Part 1 will determine if NUC-3373 should be administered with LV. Part 2 consists of a dose escalation phase, to assess the safety/tolerability of different doses of NUC-3373 in combination with either oxaliplatin (NUFOX) or irinotecan (NUFIRI), and an expansion phase, to assess weekly schedules of NUFOX and NUFIRI regimens selected in the escalation phase. Part 3 will assess the safety/efficacy of NUFOX and NUFIRI regimens administered in combination with bevacizumab, cetuximab or panitumumab. Additional patients may be enrolled in all parts to replace patients who withdraw prior to completing the 28-day safety evaluation period to complete the min number patients per cohort. Enrolment may be expanded at the DSMCs discretion.

Arm	Type	Receives
NUC-3373 + leucovorin (LV) every other week	Experimental	Drug: NUC-3373 + leucovorinArm 1a: NUC-3373 administered IV followed by a 2-week washout period. The next dose of NUC-3373 administered in combination with LV at 400 mg/m2. All subsequent doses of NUC-3373 administered in combination with LV every 2 weeks in 28-day cycles.
NUC-3373 every other week	Experimental	Drug: NUC-3373Arm 1b: LV 400 mg/m2 administered IV over 2 hours prior to NUC-3373 infusion followed by a 2-week washout period. Then, NUC-3373 administered IV every 2 weeks without LV in 28-day cycles.
NUC-3373 + leucovorin (LV) weekly	Experimental	Drug: NUC-3373 + leucovorinArm 1c: LV 400 mg/m2 administered IV over 2 hours followed by NUC-3373 administered IV weekly on Days 1, 8, 15 and 22 of 28-day cycles.
NUC-3373 + leucovorin (LV); combination chemotherapy ineligible	Experimental	Drug: NUC-3373 + leucovorinArm 1d: LV 400 mg/m2 administered IV over 2 hours followed by NUC-3373 administered IV on Days 1, 8, 15 and 22 of 28-day cycles.
NUC-3373 + oxaliplatin weekly	Experimental	Drug: NUFOXArm 2a: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with oxaliplatin (85 mg/m2) administered on Days 1 and 15.
NUC-3373 + irinotecan weekly	Experimental	Drug: NUFIRIArm 2b: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with irinotecan (180 mg/m2) on Days 1 and 15.
NUC-3373 + oxaliplatin (NUFOX) expansion	Experimental	Drug: NUFOXArm 2c: At the completion of Arm 2a, the recommended dose of NUC-3373 (+LV 400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with oxaliplatin (85 mg/m2) administered on Days 1 and 15.
NUC-3373 + irinotecan (NUFIRI) expansion	Experimental	Drug: NUFIRIArm 2d: At the completion of Arm 2b, the recommended dose of NUC-3373 (+LV 400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with irinotecan (180 mg/m2) on Days 1 and 15.
NUFOX + bevacizumab weekly	Experimental	Drug: NUFOX + VEGF pathway inhibitorArm 3a: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a will be combined with bevacizumab. NUC-3373+LV will be administered weekly, oxaliplatin and bevacizumab will be administered every other week.
NUFOX + bevacizumab every other week	Experimental	Drug: NUFOX + VEGF pathway inhibitorArm 3b: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a will be combined with bevacizumab. NUC-3373+LV+oxaliplatin+bevacizumab will be administered every other week.
NUFIRI + bevacizumab weekly	Experimental	Drug: NUFIRI + VEGF pathway inhibitorArm 3c: NUC-3373, LV and irinotecan at dose levels used in Arm 2b will be combined with bevacizumab. NUC-3373+LV will be administered weekly, irinotecan and bevacizumab will be administered every other week.
NUFIRI + bevacizumab every other week	Experimental	Drug: NUFIRI + VEGF pathway inhibitorArm 3d: NUC-3373, LV and irinotecan at dose levels used in Arm 2b will be combined with bevacizumab. NUC-3373+LV+irinotecan+bevacizumab will be administered every other week.
NUC-3373 + LV + bevacizumab; maintenance patients	Experimental	Drug: NUC-3373 + bevacizumabArm 3e: NUC-3373+LV (400 mg/m2) administered weekly on Days 1, 8, 15 and 22 of 28-day cycles in combination with bevacizumab (administered every other week).
NUFOX + cetuximab	Experimental	Drug: NUFOX + EGFR inhibitorArm 3f: NUC-3373, LV and oxaliplatin at dose levels used in Arm 2a may be administered in subsequent cetuximab cohorts. NUC-3373+LV may be administered weekly or every other week, oxaliplatin will be administered every other week and cetuximab will be administered weekly.
NUFIRI + cetuximab	Experimental	Drug: NUFIRI + EGFR inhibitorArm 3g: NUC-3373, LV and irinotecan at dose levels used in Arm 2b may be administered in subsequent cetuximab cohorts. NUC-3373+LV may be administered weekly or every other week, irinotecan will be administered every other week and cetuximab will be administered weekly.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (39 listed)

All patients
Provision of written informed consent
Have histological confirmation of CRC with evidence of locally advanced/unresectable or metastatic disease
Age ≥18 years
Life expectancy of ≥12 weeks

Key exclusion criteria (37 listed)

All patients
Prior history of hypersensitivity or current contra-indications to 5-FU or capecitabine
Prior history of hypersensitivity or current contra-indications to any of the combination agents required for the study arm to which the patient is assigned
History of allergic reactions attributed to the components of the NUC-3373 drug product formulation
Symptomatic CNS or leptomeningeal metastases

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NUC-3373 + leucovorinAlso: folinic acid, levoleucovorin, Nucleotide analogueNUC-3373 + leucovorin	Drug	NUC-3373 + leucovorin (LV) every other week, NUC-3373 + leucovorin (LV) weekly, NUC-3373 + leucovorin (LV); combination chemotherapy ineligible
NUC-3373Also: Nucleotide analogueNUC-3373	Drug	NUC-3373 every other week
NUFOXAlso: Eloxatin, Nucleotide analogueNUC-3373 + oxaliplatin	Drug	NUC-3373 + oxaliplatin (NUFOX) expansion, NUC-3373 + oxaliplatin weekly
NUFOX + VEGF pathway inhibitorAlso: Eloxatin, Avastin, Nucleotide analogueNUC-3373 + oxaliplatin + bevacizumab	Drug	NUFOX + bevacizumab every other week, NUFOX + bevacizumab weekly
NUFOX + EGFR inhibitorAlso: Eloxatin, Erbitux, Nucleotide analogue, VectibixNUC-3373 + oxaliplatin + cetuximab/panitumumab	Drug	NUFOX + cetuximab
NUFIRIAlso: Campto, Camptosar, Nucleotide analogueNUC-3373 + irinotecan	Drug	NUC-3373 + irinotecan (NUFIRI) expansion, NUC-3373 + irinotecan weekly
NUFIRI + VEGF pathway inhibitorAlso: Campto, Camptosar, Avastin, Nucleotide analogueNUC-3373 + irinotecan + bevacizumab	Drug	NUFIRI + bevacizumab every other week, NUFIRI + bevacizumab weekly
NUFIRI + EGFR inhibitorAlso: Campto, Camptosar, Erbitux, Nucleotide analogueNUC-3373 + irinotecan + cetuximab/panitumumab	Drug	NUFIRI + cetuximab
NUC-3373 + bevacizumabAlso: Nucleotide analogue, AvastinNUC-3373 + bevacizumab	Drug	NUC-3373 + LV + bevacizumab; maintenance patients

Primary outcome

Percentage Change From Baseline in Tumour Size
Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Efficacy (per RECIST v 1.1): defined as the best percentage change from baseline in tumour size (mm)
Disease Control Rate (DCR)
Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Efficacy (per RECIST v 1.1): defined as the proportion of patients achieving confirmed response (CR and PR) or stable disease (SD) as the best overall response
Duration of Stable Disease (DoSD)
Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Efficacy (per RECIST v 1.1): defined as the time from the time measurement criteria are first met for SD until the first date that recurrence or progressive disease (PD) is objectively documented
Progression Free Survival (PFS)
Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Efficacy (per RECIST v 1.1): defined as the time from first dose of study treatment until the date of objective disease progression or death
Overall Survival (OS)
Time frame: From the date of randomization until the date of death from any cause, until the end of study (up to 25 months)]
Efficacy: defined as the time from randomization until the date of death from any cause
Best Overall Response
Time frame: Assessed every 8 weeks from Day 1 until the end of study (up to 25 months)
Best overall response to study treatment according to RECIST v1.1

Results and safety

Results posted to the registry on 23 Apr 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
NUC-3373 + Leucovorin (LV) Every Other Week	11	0
NUC-3373 Every Other Week	11	0
NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly	12	0
NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly	6	0
NUC-3373 + Leucovorin (LV); Combination Chemotherapy Ineligible	0	0
NUC-3373 + Oxaliplatin Weekly	23	0
NUC-3373 + Irinotecan Weekly	25	0
NUC-3373 + Irinotecan Weekly (PK Sub-study)	9	0
NUC-3373 + Oxaliplatin (NUFOX) Expansion	0	0
NUC-3373 + Irinotecan (NUFIRI) Expansion	0	0
NUFOX + Bevacizumab Weekly	5	0
NUFOX + Bevacizumab Every Other Week	0	0
NUFIRI + Bevacizumab Weekly	9	0
NUFIRI + Bevacizumab Every Other Week	0	0
NUC-3373 + LV + Bevacizumab; Maintenance Patients	0	0
NUFOX + Cetuximab	0	0
NUFIRI + Cetuximab	0	0

Primary outcome: Percentage Change From Baseline in Tumour Size

Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months). Median (Full Range). Unit: Percent change

Measure	NUC-3373 + Leucovorin (LV) Every Other Week n = 0	NUC-3373 Every Other Week n = 4	NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly n = 5	NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly n = 2	NUC-3373 + Oxaliplatin Weekly n = 8	NUC-3373 + Irinotecan Weekly n = 9	NUC-3373 + Irinotecan Weekly (PK Sub-study) n = 2	NUFOX + Bevacizumab Weekly n = 4	NUFIRI + Bevacizumab Weekly n = 8
Value	–	8.3 (-15 to 20)	2.9 (-28 to 15)	3.2 (-3 to 9)	2.3 (-19 to 10)	7.9 (-12 to 21)	2.8 (-2 to 8)	-13.9 (-18 to -12)	-11.1 (-26 to 5)

Population analysed: Evaluable for Response (EFR): Patients with measurable disease at baseline who received at least two cycles of study treatment (receiving at least 75% of the planned doses over the two cycles) and had a post-treatment objective disease assessment. Data are only available for patients in the EFR set who did not have a best response of progressive disease and who had evaluable post-dose target lesion data. All patients in Arm 1a had a best response of either progressive disease or non-evaluable.

Primary outcome: Disease Control Rate (DCR)

Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months). Number. Unit: percentage of patients

Measure	NUC-3373 + Leucovorin (LV) Every Other Week n = 3	NUC-3373 Every Other Week n = 7	NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly n = 8	NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly n = 4	NUC-3373 + Oxaliplatin Weekly n = 15	NUC-3373 + Irinotecan Weekly n = 14	NUC-3373 + Irinotecan Weekly (PK Sub-study) n = 6	NUFOX + Bevacizumab Weekly n = 5	NUFIRI + Bevacizumab Weekly n = 9
Value	0	42.9	62.5	50	46.7	42.9	33.3	80.0	88.9

Population analysed: Evaluable for Response (EFR): Patients with measurable disease at baseline who received at least two cycles of study treatment (receiving at least 75% of the planned doses over the two cycles) and had a post-treatment objective disease assessment. Data are only available for patients in the EFR set achieving confirmed response (CR and PR) or stable disease (SD) as the best overall response.

Primary outcome: Duration of Stable Disease (DoSD)

Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months). Median (Full Range). Unit: months

Measure	NUC-3373 + Leucovorin (LV) Every Other Week n = 0	NUC-3373 Every Other Week n = 3	NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly n = 5	NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly n = 2	NUC-3373 + Oxaliplatin Weekly n = 7	NUC-3373 + Irinotecan Weekly n = 6	NUC-3373 + Irinotecan Weekly (PK Sub-study) n = 2	NUFOX + Bevacizumab Weekly n = 4	NUFIRI + Bevacizumab Weekly n = 8
Value	–	1.9 (1.9 to 4.8)	2.6 (0.03 to 3.3)	1.9 (1.9 to 1.9)	3.7 (0.03 to 4.4)	3.2 (2.0 to 8.6)	2.3 (2.0 to 2.5)	6.5 (5.3 to 7.9)	4.6 (0.2 to 13.2)

Primary outcome: Progression Free Survival (PFS)

Time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months). Median (Full Range). Unit: months

Measure	NUC-3373 + Leucovorin (LV) Every Other Week n = 10	NUC-3373 Every Other Week n = 11	NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly n = 11	NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly n = 6	NUC-3373 + Oxaliplatin Weekly n = 23	NUC-3373 + Irinotecan Weekly n = 23	NUC-3373 + Irinotecan Weekly (PK Sub-study) n = 8	NUFOX + Bevacizumab Weekly n = 5	NUFIRI + Bevacizumab Weekly n = 9
Value	1.7 (0.03 to 2.1)	2.3 (0.03 to 4.2)	2.9 (0.03 to 5.0)	1.8 (0.03 to 3.6)	2.5 (0.03 to 6.1)	3.6 (0.03 to 6.5)	2.0 (0.03 to 4.1)	7.7 (2.3 to 9.8)	5.5 (1.9 to 15.0)

Population analysed: Patients who received at least one dose of NUC-3373

Adverse events

Time frame: Each patient was assessed for serious and other (non-serious) adverse events from the date of consent until 30 days after the last dose of study treatment, up to 25 months. Each patient was assessed for all-cause mortality from the date of randomization until the date of death from any cause, up to 25 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
NUC-3373 + Leucovorin (LV) Every Other Week	6 of 10 (60%)	10 of 10 (100%)	3 of 11
NUC-3373 Every Other Week	2 of 11 (18.2%)	11 of 11 (100%)	4 of 11
NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly	3 of 11 (27.3%)	11 of 11 (100%)	1 of 12
NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6
NUC-3373 + Oxaliplatin Weekly	11 of 23 (47.8%)	23 of 23 (100%)	11 of 23
NUC-3373 + Irinotecan Weekly	8 of 23 (34.8%)	23 of 23 (100%)	11 of 25
NUC-3373 + Irinotecan Weekly (PK Sub-study)	2 of 8 (25%)	8 of 8 (100%)	6 of 9
NUFOX + Bevacizumab Weekly	4 of 5 (80%)	5 of 5 (100%)	3 of 5
NUFIRI + Bevacizumab Weekly	4 of 9 (44.4%)	9 of 9 (100%)	4 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Elisabeth Oelmann, MD PhD study director

NuCana plc

10 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing NUC-3373 + leucovorin, NUC-3373 and NUFOX in people with Colorectal Cancer and Colorectal Neoplasms, run by NuCana plc at 10 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 39 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States, United Kingdom, France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage Change From Baseline in Tumour Size (time frame: Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03428958.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2025.