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CompletedNCT03428958Updated Apr 23, 2025Results posted

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

A Phase 1/2 interventional study of NUC-3373 + leucovorin and NUC-3373 in Colorectal Cancer, Colorectal Neoplasms and Colorectal Carcinoma, sponsored by NuCana plc. Completed at 10 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-23.

Sponsored by NuCana plc · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
111
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Where this study stands

Counted across the records on this site · 2026-11-12

Among 64 studies testing leucovorin in Colorectal Neoplasms — 4 open to participants now, 7 under way, 1 of them phase 3. Leucovorin · Colorectal Neoplasms.

Enrollment
23rd of 62
111 · median 56
Started
2018
with 1 other
Phase 1/2
7 of 64
1 open now
Registered
57th of 64
by date

Among the 64 studies testing leucovorin in Colorectal Neoplasms, this one is the 23rd largest by enrollment of the 62 interventional ones that give a count, is one of 2 that started in 2018, is one of 7 in phase 1/2, and was the 57th registered.

Colorectal Neoplasms

6,541 studies on the registry are indexed under Colorectal Neoplasms; 1,667 are open to participants now.

Browse Colorectal Neoplasms studies →

Open to participants now

4 of the 64 studies testing leucovorin in Colorectal Neoplasms are open now, in 3 countries. Recruiting first, the newest first:

By country, each count listing its studies:

China1
Italy1
United States1

All 4 open studies →

About leucovorin

Leucovorin: first FDA approval 1952 (LEUCOVORIN CALCIUM). What it is approved for, and how studies give it, is on its page →

Who these studies take

Of the 1,185 Colorectal Neoplasms studies recruiting now, 769 (65%) set no upper age limit and 265 (22%) stop at 75 or younger; 48 take children under 18; 123 take healthy volunteers.

This study: 18 Years and older · all sexes · no healthy volunteers.

The full table on the hub →

This tab as a report to print or save as PDF → With an account.

Was this useful?
Watch this landscapeDownload CSVNarrow it in search →With an account: a weekly mail of what changed among 64 studies testing leucovorin in Colorectal Neoplasms, or all of them as a file.
02

Study 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). The primary objective is to identify a recommended dose and schedule for NUC-3373 when combined with these agents.

03

Conditions studied

  • Colorectal Cancer
  • Colorectal Neoplasms
  • Colorectal Carcinoma
  • Colorectal Tumors
  • Neoplasms, Colorectal

Keywords

  • Relapsed metastatic adenocarcinoma of colon/rectum
04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

All patients

  1. Provision of written
  2. Have histological confirmation of CRC with evidence of locally advanced/unresectable or disease
  3. Age ≥18 years
  4. of ≥12 weeks
  5. Performance status 0 or 1
  6. as defined by v1.1
  7. 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
  8. Adequate bone marrow function as defined by: ≥1.5×10\^9/L, count ≥100×10\^9/L (with no evidence of bleeding), and ≥9 g/dL
  9. Adequate liver function as defined by serum total ≤1.5×, and ALT ≤2.5×ULN (or ≤5×ULN if liver metastases present)
  10. Adequate renal function assessed as serum creatinine \<1.5×ULN or ≥50 mL/min. This criterion does not apply to Arm 1d.
  11. Serum albumin ≥3 g/dL
  12. For the cohort in which the patient will participate, there are no to receiving the approved partner combination drugs
  13. Ability to comply with protocol requirements
  14. Female patients of 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 , one of which must be a barrier method.
  15. 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
  16. 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

> patients

  1. 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.
  2. Patients due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
  3. Patients due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based therapy

2nd-/3rd-line patients

  1. 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
  2. Patients in Part 2 due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
  3. Patients in Part 2 due to receive NUFIRI should be suitable for re-challenge with an irinotecan-based regimen

Combination chemotherapy ineligible patients

  1. May have received one prior fluoropyrimidine-containing regimen for locally advanced or metastatic CRC
  2. Ineligible to receive combination therapy for locally advanced or metastatic CRC
  3. >30mL/min

Rapid progressors

  1. 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.
  2. Have had tumour progression ≤3 months of starting the last fluoropyrimidine-containing regimen
  3. Patients due to receive NUFOX should be suitable for re-challenge with an oxaliplatin-based regimen
  4. 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

  1. Received at least 12 weeks of 1st-line SoC therapy for locally advanced or metastatic CRC and achieved at least stable disease
  2. Eligible for maintenance therapy

Exclusion criteria

Exclusion Criteria:

All patients

  1. Prior history of or current to 5-FU or capecitabine
  2. 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
  3. History of allergic reactions attributed to the components of the NUC-3373 drug product formulation
  4. Symptomatic CNS or
  5. Symptomatic ascites, ascites currently requiring drainage procedures or ascites requiring drainage over the prior 3 months
  6. Chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy [e.g. for bone pain]), immunotherapy or exposure to another 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
  7. Residual toxicities from prior chemotherapy or radiotherapy, which have not regressed to Grade ≤1 severity ( v5.0) except for alopecia. In cohorts not containing oxaliplatin, residual Grade 2 neuropathy is allowed.
  8. History of another 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.
  9. Presence of active bacterial or viral infection (including SARS-CoV-2, Herpes Zoster or chicken pox), known positive or known active or C
  10. 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
  11. 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 and undergo study procedures
  12. Currently pregnant, lactating or breastfeeding
  13. >450 milliseconds for males and >470 milliseconds for females
  14. Required concomitant use of drugs known to prolong QT/QTc interval
  15. Required concomitant use of strong 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
  16. For patients receiving irinotecan: Use of strong UGT1A1 inhibitors within 1 week of first receipt of study drug
  17. Has received a within four weeks of first planned dose of study medication
  18. Known DPD or TYMP mutations associated with toxicity to fluoropyrimidines
  19. 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

  1. Patients with a history of haemoptysis (≥1/2 tsp of red blood)
  2. Wound healing complications or surgery within 28 days of starting bevacizumab
  3. Severe chronic wounds, ulcers or bone fracture
  4. Arterial thromboembolic events or haemorrhage within 6 months prior to study entry (except for tumour bleeding surgically treated by tumour resection)
  5. Bleeding diatheses or coagulopathy
  6. Receiving full-dose anti-coagulation treatment
  7. Uncontrolled hypertension
  8. coronary heart disease or myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia
  9. Severe proteinuria
  10. Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhoea
  11. Any contraindications present in the bevacizumab Prescribing Information

Patients receiving cetuximab or panitumumab

  1. Clinically significant coronary heart disease or myocardial infarction within the last 12 months or high risk of uncontrolled arrhythmia
  2. Acute or subacute ileus, chronic inflammatory bowel disease or chronic diarrhoea
  3. Hypomagnesaemia or hypokalaemia not controlled by oral therapy
  4. Any contraindications present in the cetuximab or panitumumab Prescribing Information
Terms in these criteria, in plain language(29)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
111 participants (actual)

Study arms

  • Experimental
    NUC-3373 + leucovorin (LV) every other week

    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.

    Drug: NUC-3373 + leucovorin

  • Experimental
    NUC-3373 every other week

    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.

    Drug: NUC-3373

  • Experimental
    NUC-3373 + leucovorin (LV) weekly

    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.

    Drug: NUC-3373 + leucovorin

  • Experimental
    NUC-3373 + leucovorin (LV); combination chemotherapy ineligible

    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.

    Drug: NUC-3373 + leucovorin

  • Experimental
    NUC-3373 + oxaliplatin weekly

    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.

    Drug: NUFOX

  • Experimental
    NUC-3373 + irinotecan weekly

    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.

    Drug: NUFIRI

  • Experimental
    NUC-3373 + oxaliplatin (NUFOX) expansion

    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.

    Drug: NUFOX

  • Experimental
    NUC-3373 + irinotecan (NUFIRI) expansion

    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.

    Drug: NUFIRI

  • Experimental
    NUFOX + bevacizumab weekly

    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.

    Drug: NUFOX + VEGF pathway inhibitor

  • Experimental
    NUFOX + bevacizumab every other week

    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.

    Drug: NUFOX + VEGF pathway inhibitor

  • Experimental
    NUFIRI + bevacizumab weekly

    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.

    Drug: NUFIRI + VEGF pathway inhibitor

  • Experimental
    NUFIRI + bevacizumab every other week

    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.

    Drug: NUFIRI + VEGF pathway inhibitor

  • Experimental
    NUC-3373 + LV + bevacizumab; maintenance patients

    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).

    Drug: NUC-3373 + bevacizumab

  • Experimental
    NUFOX + cetuximab

    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.

    Drug: NUFOX + EGFR inhibitor

  • Experimental
    NUFIRI + cetuximab

    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.

    Drug: NUFIRI + EGFR inhibitor

Interventions

  • DrugNUC-3373 + leucovorin

    Drug pages: Fosifloxuridine nafalbenamide · Leucovorin

    NUC-3373 + leucovorin

    Also known as: folinic acid, levoleucovorin, Nucleotide analogue

  • DrugNUC-3373

    NUC-3373

    Also known as: Nucleotide analogue

  • DrugNUFOX

    NUC-3373 + oxaliplatin

    Also known as: Eloxatin, Nucleotide analogue

  • DrugNUFOX + VEGF pathway inhibitor

    Drug page: Oxaliplatin

    NUC-3373 + oxaliplatin + bevacizumab

    Also known as: Eloxatin, Avastin, Nucleotide analogue

  • DrugNUFOX + EGFR inhibitor

    Drug page: Oxaliplatin

    NUC-3373 + oxaliplatin + cetuximab/panitumumab

    Also known as: Eloxatin, Erbitux, Nucleotide analogue, Vectibix

  • DrugNUFIRI

    NUC-3373 + irinotecan

    Also known as: Campto, Camptosar, Nucleotide analogue

  • DrugNUFIRI + VEGF pathway inhibitor

    Drug page: Irinotecan

    NUC-3373 + irinotecan + bevacizumab

    Also known as: Campto, Camptosar, Avastin, Nucleotide analogue

  • DrugNUFIRI + EGFR inhibitor

    Drug page: Irinotecan

    NUC-3373 + irinotecan + cetuximab/panitumumab

    Also known as: Campto, Camptosar, Erbitux, Nucleotide analogue, Vectibix

  • DrugNUC-3373 + bevacizumab

    Drug pages: Fosifloxuridine nafalbenamide · Bevacizumab

    NUC-3373 + bevacizumab

    Also known as: Nucleotide analogue, Avastin

06

What researchers measure

Primary outcomes

  1. 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)

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

  2. 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

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

  3. 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

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

  4. 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

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

  5. Overall Survival (OS)

    Efficacy: defined as the time from randomization until the date of death from any cause

    Time frame: From the date of randomization until the date of death from any cause, until the end of study (up to 25 months)]

  6. Best Overall Response

    Best overall response to study treatment according to RECIST v1.1

    Time frame: Assessed every 8 weeks from Day 1 until the end of study (up to 25 months)

07

Results

Posted Apr 23, 2025

Participant flow

A total of 111 patients were recruited between July 2018 and June 2023.

Participant flow — Overall Study
MilestoneNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Leucovorin (LV); Combination Chemotherapy IneligibleNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUC-3373 + Oxaliplatin (NUFOX) ExpansionNUC-3373 + Irinotecan (NUFIRI) ExpansionNUFOX + Bevacizumab WeeklyNUFOX + Bevacizumab Every Other WeekNUFIRI + Bevacizumab WeeklyNUFIRI + Bevacizumab Every Other WeekNUC-3373 + LV + Bevacizumab; Maintenance PatientsNUFOX + CetuximabNUFIRI + Cetuximab
Started1111126023259005090000
Completed00000000000000000
Not completed1111126023259005090000
Withdrew: Adverse event00010210000000000
Withdrew: Clinical progression23210200000000000
Withdrew: Progression per recist66740780000010000
Withdrew: Death22000796003040000
Withdrew: Lost to follow-up00000110000000000
Withdrew: Physician/sponsor decision10100222002040000
Withdrew: Withdrawal by subject00200241000000000

Outcome measures

PrimaryPercentage Change From Baseline in Tumour Size

Efficacy (per RECIST v 1.1): defined as the best percentage change from baseline in tumour size (mm)

Time frame:
Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Reported as:
Median · Percent change
Percentage Change From Baseline in Tumour Size
Percent changeNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
Percentage Change From Baseline in Tumour Size—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)
PrimaryDisease 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

Time frame:
Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Reported as:
Number · percentage of patients
Disease Control Rate (DCR)
percentage of patientsNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
Disease Control Rate (DCR)042.962.55046.742.933.380.088.9
PrimaryDuration 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

Time frame:
Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Reported as:
Median · months
Duration of Stable Disease (DoSD)
monthsNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
Duration of Stable Disease (DoSD)—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)
PrimaryProgression 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

Time frame:
Assessed every 8 weeks following Day 1 until the end of study (up to 25 months)
Reported as:
Median · months
Progression Free Survival (PFS)
monthsNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
Progression Free Survival (PFS)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)
PrimaryOverall Survival (OS)

Efficacy: defined as the time from randomization until the date of death from any cause

Time frame:
From the date of randomization until the date of death from any cause, until the end of study (up to 25 months)]
Reported as:
Median · months
Overall Survival (OS)
monthsNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
Overall Survival (OS)1.9 (0.9 to 3.3)3.0 (1.5 to 7.7)3.6 (0.8 to 8.0)3.6 (1.3 to 5.5)3.4 (0.4 to 24.5)3.2 (0.5 to 19.1)7.3 (1.4 to 13.6)14.2 (9.4 to 16.9)12.8 (3.2 to 18.2)
PrimaryBest Overall Response

Best overall response to study treatment according to RECIST v1.1

Time frame:
Assessed every 8 weeks from Day 1 until the end of study (up to 25 months)
Reported as:
Number · percentage of participants
Best Overall Response
percentage of participantsNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
Complete Response000000000
Partial Response000000000
Stable Disease042.962.55046.742.933.380.088.9
Progressive Disease100.042.937.550.046.742.966.720.011.1
Not Evaluable014.3006.714.3000

Adverse events

Collected over 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.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
NUC-3373 + Leucovorin (LV) Every Other Week3/11 (27.3%)6/10 (60%)10/10 (100%)
NUC-3373 Every Other Week4/11 (36.4%)2/11 (18.2%)11/11 (100%)
NUC-3373 (1500 mg/m2) + Leucovorin (LV) Weekly1/12 (8.3%)3/11 (27.3%)11/11 (100%)
NUC-3373 (2500 mg/m2) + Leucovorin (LV) Weekly0/6 (0%)2/6 (33.3%)6/6 (100%)
NUC-3373 + Oxaliplatin Weekly11/23 (47.8%)11/23 (47.8%)23/23 (100%)
NUC-3373 + Irinotecan Weekly11/25 (44%)8/23 (34.8%)23/23 (100%)
NUC-3373 + Irinotecan Weekly (PK Sub-study)6/9 (66.7%)2/8 (25%)8/8 (100%)
NUFOX + Bevacizumab Weekly3/5 (60%)4/5 (80%)5/5 (100%)
NUFIRI + Bevacizumab Weekly4/9 (44.4%)4/9 (44.4%)9/9 (100%)
Most frequent serious events
Showing 10 of 46
Most frequent serious events
EventNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
NauseaGastrointestinal disorders0/100/110/110/61/232/230/82/51/9
VomitingGastrointestinal disorders0/100/110/110/62/231/230/82/51/9
Lower respiratory tract infectionInfections and infestations3/100/110/110/61/230/230/80/50/9
AscitesGastrointestinal disorders0/100/110/110/61/230/230/81/50/9
Drain site complicationInjury, poisoning and procedural complications0/100/110/110/60/230/230/81/50/9
HypokalaemiaMetabolism and nutrition disorders0/100/110/110/60/230/230/81/50/9
Back painMusculoskeletal and connective tissue disorders0/100/110/110/60/230/230/81/51/9
PyrexiaGeneral disorders0/100/111/111/60/230/230/80/50/9
Urinary tract infectionInfections and infestations1/100/110/111/60/230/230/80/50/9
Febrile neutropeniaBlood and lymphatic system disorders0/100/110/110/60/230/231/80/50/9
Most frequent other events
Showing 10 of 178
Most frequent other events
EventNUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUFOX + Bevacizumab WeeklyNUFIRI + Bevacizumab Weekly
NauseaGastrointestinal disorders2/103/117/114/613/2313/234/85/55/9
FatigueGeneral disorders3/102/111/115/615/238/238/84/56/9
Peripheral sensory neuropathyNervous system disorders0/100/110/110/61/230/230/85/51/9
DiarrhoeaGastrointestinal disorders3/104/113/111/610/2315/234/84/58/9
VomitingGastrointestinal disorders1/102/118/114/613/238/232/84/55/9
AnaemiaBlood and lymphatic system disorders0/102/114/111/610/2310/233/83/53/9
ConstipationGastrointestinal disorders2/101/114/110/68/234/234/83/52/9
HypertensionVascular disorders0/100/110/110/60/231/231/83/53/9
Alanine aminotransferase increasedInvestigations0/101/112/111/66/232/231/80/55/9
Aspartate aminotransferase increasedInvestigations0/100/111/111/65/234/231/80/55/9

Baseline characteristics

No patients recruited to Arms 1d, 2c, 3b, 3d, 3e, 3f, and 3g.

Age, Continuous
Age, Continuous(Years)NUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Leucovorin (LV); Combination Chemotherapy IneligibleNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUC-3373 + Oxaliplatin (NUFOX) ExpansionNUC-3373 + Irinotecan (NUFIRI) ExpansionNUFOX + Bevacizumab WeeklyNUFOX + Bevacizumab Every Other WeekNUFIRI + Bevacizumab WeeklyNUFIRI + Bevacizumab Every Other WeekNUC-3373 + LV + Bevacizumab; Maintenance PatientsNUFOX + CetuximabNUFIRI + CetuximabTotal
Mean55.1 ± 13.259.1 ± 9.355.4 ± 10.256.0 ± 11.0—58.3 ± 10.056.7 ± 10.155.3 ± 10——65 ± 5.9—54.3 ± 14.2————57 ± 10.5
Sex: Female, Male
Sex: Female, Male(Participants)NUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Leucovorin (LV); Combination Chemotherapy IneligibleNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUC-3373 + Oxaliplatin (NUFOX) ExpansionNUC-3373 + Irinotecan (NUFIRI) ExpansionNUFOX + Bevacizumab WeeklyNUFOX + Bevacizumab Every Other WeekNUFIRI + Bevacizumab WeeklyNUFIRI + Bevacizumab Every Other WeekNUC-3373 + LV + Bevacizumab; Maintenance PatientsNUFOX + CetuximabNUFIRI + CetuximabTotal
Female4544—12107——2—3————51
Male7682—11152——3—6————60
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)NUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Leucovorin (LV); Combination Chemotherapy IneligibleNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUC-3373 + Oxaliplatin (NUFOX) ExpansionNUC-3373 + Irinotecan (NUFIRI) ExpansionNUFOX + Bevacizumab WeeklyNUFOX + Bevacizumab Every Other WeekNUFIRI + Bevacizumab WeeklyNUFIRI + Bevacizumab Every Other WeekNUC-3373 + LV + Bevacizumab; Maintenance PatientsNUFOX + CetuximabNUFIRI + CetuximabTotal
Hispanic or Latino0010—111——0—0————4
Not Hispanic or Latino1111106—21218——4—7————99
Unknown or Not Reported0010—130——1—2————8
Race (NIH/OMB)
Race (NIH/OMB)(Participants)NUC-3373 + Leucovorin (LV) Every Other WeekNUC-3373 Every Other WeekNUC-3373 (1500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 (2500 mg/m2) + Leucovorin (LV) WeeklyNUC-3373 + Leucovorin (LV); Combination Chemotherapy IneligibleNUC-3373 + Oxaliplatin WeeklyNUC-3373 + Irinotecan WeeklyNUC-3373 + Irinotecan Weekly (PK Sub-study)NUC-3373 + Oxaliplatin (NUFOX) ExpansionNUC-3373 + Irinotecan (NUFIRI) ExpansionNUFOX + Bevacizumab WeeklyNUFOX + Bevacizumab Every Other WeekNUFIRI + Bevacizumab WeeklyNUFIRI + Bevacizumab Every Other WeekNUC-3373 + LV + Bevacizumab; Maintenance PatientsNUFOX + CetuximabNUFIRI + CetuximabTotal
American Indian or Alaska Native0001—000——0—0————1
Asian0010—121——1—1————7
Native Hawaiian or Other Pacific Islander0000—100——0—0————1
Black or African American1100—020——0—1————5
White1010105—20198——4—7————93
More than one race0000—000——0—0————0
Unknown or Not Reported0010—120——0—0————4
08

Study locations

10 sites
  • Beth Israel Deaconess Medical Center
    Boston, Massachusetts 02215, United States
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Vanderbilt University
    Nashville, Tennessee 37232, United States
  • Seattle Cancer Center
    Seattle, Washington 98109-1023, United States
  • Compass Oncology
    Vancouver, Washington 98684, United States
  • Hopital Franco-Britannique
    Levallois-Perret, 92300, France
  • The Beatson West of Scotland Cancer Centre
    Glasgow, G12 0YN, United Kingdom
  • University College London Hospitals NHS Foundation Trust
    London, W1T 7HA, United Kingdom
  • University of Oxford
    Oxford, OX3 7LE, United Kingdom
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Oct 2018 to primary completion in Mar 2024, 65 months.

Results were first posted in Apr 2025, 1 year 1 month after primary completion.

Of 102 non-industry phase 1/2 interventional studies under Colorectal Neoplasms, half reached primary completion within 57 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 106. This study's 65 months is above that.

Counting every sponsor, half of 260 studies reached it within 59 months; a quarter within 36 and three quarters within 87.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 2, 2018
First posted
Feb 12, 2018
StartActual
Oct 5, 2018
Primary completionActual
Mar 19, 2024
CompletionActual
Mar 21, 2024
Results first posted
Apr 23, 2025
Last update
Apr 23, 2025
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 23, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03428958
Lead sponsor
NuCana plc
Responsible party
Sponsor
First posted
Feb 12, 2018
Start date
Oct 5, 2018
Primary completion
Mar 19, 2024
Completion
Mar 21, 2024
Results posted
Apr 23, 2025
Last update
Apr 23, 2025

Study contacts

Elisabeth Oelmann, MD PhD
study director · NuCana plc

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Fosifloxuridine nafalbenamide · Leucovorin · Oxaliplatin · Irinotecan · Bevacizumab

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