CancerPhase 1NuTide:301NCT02723240

NUC-3373 in Advanced Solid Tumours

A Phase 1 study testing NUC-3373 in people with Cancer, run by University of Oxford at 3 sites in United Kingdom.

Completed

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

Trial summary

A two-part, phase I open label, dose escalation and expansion study to assess safety, pharmacokinetics and clinical activity of NUC-3373, a nucleotide analogue, in participants with advanced solid tumours. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Cancer
What is being tested?: NUC-3373
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 62 participants
Where: 3 sitesUnited Kingdom
Study dates: Jan 2016to 24 Feb 2021
Phase: Phase 1
Are there results?: None posted in the registry

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

Provision of signed written informed consent.
Diagnosis: Histologically confirmed diagnosis of solid tumour, which is not amenable to standard chemotherapy, is refractory to standard chemotherapy or for which no standard chemotherapy exists.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Life expectancy of ≥ 12 weeks.
Participants must have measurable disease per RECIST criteria and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions which do not fulfil RECIST criteria for measurable disease).

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Adequate bone marrow function as defined by: WBC of ≥ 3 x109/L, ANC of ≥ 1.5 x 109/L, platelet count of ≥ 100 x 109/L, and haemoglobin of ≥ 9g/dL.
Adequate liver function, as determined by: Serum total bilirubin ≤1.5 x ULN, AST and ALT ≤ 2.5 x ULN.
Adequate renal function as defined by serum creatinine within ≤ 1.5 x ULN upper limits of normal or calculated clearance ≥50 ml/min/1.73 m2. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (using the Cockcroft-Gault formula). For subjects with a Body Mass Index (BMI) >30 kg/m2, lean body weight should be used instead
Left Ventricular Ejection Fraction (LVEF) ≥50% on echocardiogram
Ability to comply with protocol requirements.
Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to the first scheduled IMP administration at Cycle 1 Day 1. .

Who cannot join

History of allergic reactions attributed to previous 5-FU or capecitabine treatment.
History of allergic reactions to any of the components of the diluent solutions supplied with NUC-3373.
Symptomatic CNS or leptomeningeal metastases.
Participants with a history of myocardial infarction within the last 5 years or with significant cardiac arrhythmias requiring medication or pacemaker.
Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), immunotherapy or any other anticancer agent within 28 days of first administration of the IMP.
For nitrosoureas and mitomycin C within 6 weeks of first administration of IMP.

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For hormone or biological therapy within 14 days of first administration of IMP.
Prior toxicities from chemotherapy or radiotherapy which have not regressed to Grade ≤ 1 severity (NCI-CTCAE version 4.0) apart from renal function (provided inclusion criteria 9 is met), neuropathy and alopecia.
Another active cancer excluding basal cell carcinoma or intraepithelial neoplasia (CIN/cervical in situ or melanoma in situ).
Participants with uncontrolled concomitant illness, active infection requiring i.v. antibiotics, or uncontrolled infections, or a fever >38.5°C on the day of scheduled dosing.
Participants with serious illnesses, medical conditions, or other medical history, including laboratory results, which, in the CI or delegates opinion would be likely to interfere with a participant's participation in the study, or with the interpretation of the results.
Known HIV or known active Hepatitis B or C.
Any condition (e.g. known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the CI or delegates may affect the participant's ability to sign the informed consent and undergo study procedures.
All men or women of reproductive potential, unless using at least two contraceptive precautions, one of which must be from the list below, the other must be a condom*1 or abstaining from sexual intercourse, until six months after treatment has ended:
Combined (oestrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation: either oral, intravaginal or transdermal.
Progesterone-only hormonal contraception associated with inhibition of ovulation: either oral, injectable or implantable.
Intra-uterine device (IUD)
Intra-uterine hormone-releasing system (IUS)
Bilateral tubal occlusion
Vasectomised partner*2
Sexual abstinence*3
Participants who are currently breastfeeding.

Trial locations and contacts

3 sites in 1 country.

United Kingdom3 sites

Belfast City Hospital
Belfast, BT9 7AB
Beatson, West of Scotland Cancer Centre
Glasgow, G12 OYN
Oxford University Hospitals NHS Trust
Oxford, OX3 7LE

Other trials in United Kingdom

About this study

Official title: A Two-part, Phase I Open Label, Dose Escalation and Expansion Study to Assess Safety, Pharmacokinetics and Clinical Activity of NUC-3373, a Nucleotide Analogue, in Participants With Advanced Solid Tumours

Read the detailed description

This is a two-part, Phase I dose escalation study of NUC-3373 (a pyrimidine nucleotide analogue) as a single agent, administered weekly or fortnightly as an I.V. (intravenous) infusion.

In both parts participants will undergo evaluations of the safety, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumour efficacy of NUC-3373

Participants may continue to receive NUC-3373 until disease progression or unacceptable toxicity occurs.

Part 1: Establish the RP2D (recommended phase two dose) and assess the safety and tolerability for single agent NUC-3373 administered as an I.V. infusion on day 1, 8, 15, 22 of a 28-day cycle. Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. The RP2D will be determined by dose escalation with sequential participants receiving increasing doses of NUC-3373 in a standard '3 + 3' cohort design.

Part 2: Establish the RP2D and assess the safety and tolerability for single agent NUC-3373 administered as a fortnightly I.V. infusion on day 1 and 15 of a 28-day cycle. Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. The RP2D will be determined by dose escalation with sequential participants receiving increasing doses of NUC-3373 in a standard '3 + 3' cohort design.

Finally, to assess preliminary efficacy signals and further characterise the safety profile, expansion cohorts of up to 20 additional participants per cohort will receive the RP2D of NUC-3373 as determined in Part 1 and Part 2 of the study. Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.

Conditions: Cancer
Being tested: NUC-3373
Keywords: NUC-3373, Dose escalation, Nucleotide Analogue
Medical subject headings: Neoplasms

What participants receive

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

NUC-3373Drug

Study groups in NCT02723240
Study group	Role	What they receive
Part 1 (weekly administration) NUC-3373 125mg/m2	Experimental	NUC-3373 125mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 250mg/m2	Experimental	NUC-3373 250mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 500mg/m2	Experimental	NUC-3373 500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 750mg/m2	Experimental	NUC-3373 750mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 1125mg/m2	Experimental	NUC-3373 1125mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 1500mg/m2	Experimental	NUC-3373 1500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 1875mg/m2	Experimental	NUC-3373 1875mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 2500mg/m2	Experimental	NUC-3373 2500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 1 (weekly administration) NUC-3373 3250mg/m2	Experimental	NUC-3373 3250mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 2 (two weekly administration) NUC-3373 1500mg/m2	Experimental	NUC-3373 1500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 15 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 2 (two weekly administration) NUC-3373 1875mg/m2	Experimental	NUC-3373 1875mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 15 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373
Part 2 (two weekly administration) NUC-3373 2500mg/m2	Experimental	NUC-3373 2500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 15 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs. Receives: Drug: NUC-3373

What is being measured

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

To establish the recommended Phase 2 Dose (RP2D) of NUC-3373 that will optimise the risk/benefit reward for the participants, administered weekly (Part 1) and when administered fortnightly (Part 2), as a single I.V. infusion.
The RP2D is the most appropriate dose that will optimise the risk/benefit reward for the participants. RP2D determination will take into consideration the plasma PK, PD assessments, the nature of the PK/PD relationship, any efficacy signals or any adverse events observed during the conduct of the dose-escalation and the available non clinical data.
The RP2D will be determined by dose escalation with sequential participants receiving increasing doses of NUC-3373 in a standard '3 + 3' cohort design. Dose escalation will stop when the Maximum Tolerated Dose (MTD)/RP2D have been defined for that Part or a decision is made by the Trial Management Group to halt enrolment.
Measured: To decide if the next cohort can be opened at a higher dose level, the Trial Management Group (TMG) will review available data (e.g. safety profile) once all participants in the preceding cohort have completed the first cycle through to Day 28.

Secondary outcomes (12)

Dose Limiting Toxicities (DLT) to assess the tolerability of NUC-3373
A DLT is defined, following case causality assessment of 'Definite', 'Probable', or 'Possible' and as such may be related to the IMP:
- Greater than or equal to Grade 3 non-haematological toxicity (e.g. mucositis, stomatitis and hand-foot syndrome) (excluding nausea/vomiting/diarrhoea or rash that responds to standard medical treatment or as allowed by eligibility criteria e.g. elevated LFTs in participants with liver metastases).
- Greater than or equal to Grade 3 nausea/vomiting/diarrhoea or rash that occurs despite standard medical treatment for such AEs (see 3.6.1).
- Grade 4 neutropaenia.
- Febrile neutropaenia.
- Grade 4 thrombocytopaenia.
- Inability to begin next dose of treatment within 14 days of the scheduled dosing due to unresolved toxicity related to NUC-3373.
- Either isolated or recurrent (i.e., cardiac, renal, neurologic) toxicity that is judged by the CI and/or TMG to be a DLT.
Measured: Assessment starts at first IMP administration (Cycle 1 Day 1) until the first cycle completion (Day 28)
Dose Limiting Toxicities (DLT) and SAEs/AEs to assess the safety of NUC-3373
All adverse events (AEs) using NCI-CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) v4.0 will be listed and summarised by descriptive statistics for all patients grouped by each dose level for each part. During treatment participants will be reviewed on a weekly basis during the first cycle and on the day of treatment. Additional visits may be arranged at the investigator's discretion. The categories will be AE, AE with CTCAE grade >3 and serious adverse events (SAE) related or not related to NUC-3373. Data presented throughout study completion, SAEs reviewed in real-time, TMG review all data (monthly meeting on average).
Measured: Adverse event monitoring starts at IMP administration (Day 1) until 28 days after the final dose of IMP has been administered.
Analysis of NUC-3373 metabolites in plasma to determine Area under the curve (AUC)
To determine the pharmacokinetics (PK) of NUC-3373 and key metabolites, samples taken:
- Part 1: Pre-dose sample; Then samples taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then samples taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in plasma to determine Peak Plasma Concentration (Cmax)
To determine the pharmacokinetics (PK) of NUC-3373 and key metabolites, samples taken:
- Part 1: Pre-dose sample; Then samples taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then samples taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in plasma to determine Clearance
To determine the pharmacokinetics (PK) of NUC-3373 and key metabolites, samples taken:
- Part 1: Pre-dose sample; Then samples taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then samples taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in plasma to determine plasma half T1/2
Analysis of NUC-3373 metabolites in PBMC, to determine the pharmacokinetics (PK) of NUC-3373 and key metabolites. Samples taken:
- Part 1: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC to determine Peak Plasma Concentration (Cmax)
Analysis of NUC-3373 metabolites in PBMC, to determine the pharmacokinetics (PK) of NUC-3373 and key metabolites. Samples taken:
- Part 1: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC to determine Area under the curve (AUC)
Analysis of NUC-3373 metabolites in PBMC, to determine the pharmacokinetics (PK) of NUC-3373 and key metabolites.
Samples taken:
- Part 1: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC determine plasma half T1/2
Analysis of NUC-3373 metabolites in PBMC, to determine the pharmacokinetics (PK) of NUC-3373 and key metabolites.
Samples taken:
- Part 1: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC to determine Clearance
Analysis of NUC-3373 metabolites in PBMC, to determine the pharmacokinetics (PK) of NUC-3373 and key metabolites.
Samples taken:
- Part 1: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Urine samples taken: 0-6 and 6-24 hour urine collection starting from beginning of IMP infusion.
Measured: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Measuring the ratio between the intracellular dTMP and dUMP concentrations.
For analysis on the effect of NUC-3373 on thymidylate synthetase activity in the PBMC to determine the pharmacodynamics (PD) of NUC-3373. We will use a sensitive and specific liquid chromatography-mass spectrometry method for quantification of these intracellular metabolites.
The unmodified TS (TS-U) and the TS in ternary complexes (TS-T) will be assessed using Western Blotting approach.
Samples taken:
- Part 1: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
- Part 2: Pre-dose sample; Then sample taken immediately after the drug has cleared the infusion line; then at 5 minutes; 15 minutes; 30 minutes; 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6hours \& 24 hours.
Measured: PD samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Response Evaluation Criteria in Solid Tumours (RECIST) to explore the anti-tumour activity of NUC-3373
To explore the anti-tumour activity of NUC-3373 using Response Evaluation Criteria in Solid Tumours (RECIST) criteria in combination with tumour specific evaluation criteria which incorporates the relevant tumour markers (e.g. GCIG criteria utilising the Cancer Antigen 125 (CA125))
Measured: Tumour assessment (CT scan/MRI scan) will be performed throughout study completion, every 8 weeks, an average of 6 per year.

Timeline

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

Jan 201624 Feb 2021

First posted30 Mar 2016 (estimated)
Study startJan 2016
Primary completion24 Feb 2020
Study completion24 Feb 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for CancerStudies of the same condition, open and under way.
More trials run by University of OxfordThe sponsor's other registered studies.
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
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 62 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02723240
Sponsor's protocol ID: OCTO_074
Other IDs: 2015-002250-13, 2015
Acronym: NuTide:301
Status last verified: Apr 2021
First submitted: 8 Dec 2015
Last updated: 14 Feb 2024
Results posted: No
Data monitoring committee: Yes
Individual data sharing: No

Publications

Spiliopoulou P, Kazmi F, Aroldi F, Holmes T, Thompson D, Griffiths L, Qi C, Parkes M, Lord S, Veal GJ, Harrison DJ, Coyle VM, Graham J, Jeffry Evans TR, Blagden SP. A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301). J Exp Clin Cancer Res. 2024 Apr 2;43(1):100. doi: 10.1186/s13046-024-03010-1.
PubMed 38566164

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?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Two-part, Phase I Open Label, Dose Escalation and Expansion Study to Assess Safety, Pharmacokinetics and Clinical Activity of NUC-3373, a Nucleotide Analogue, in Participants With Advanced Solid Tumours
ClinicalTrials.gov ID: NCT02723240
Acronym / sponsor ID: NuTide:301 / OCTO_074
Conditions: Cancer
Keywords: NUC-3373, Dose escalation, Nucleotide Analogue
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 62 participants (actual)
Lead sponsor: University of OxfordUniversity, hospital or other
Study start: Jan 2016
Primary completion: 24 Feb 2020 (actual)
Study completion: 24 Feb 2021 (actual)
First posted: 30 Mar 2016 (estimated)
Results: Not posted in the source record

Clinical summary

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

Detailed description

This is a two-part, Phase I dose escalation study of NUC-3373 (a pyrimidine nucleotide analogue) as a single agent, administered weekly or fortnightly as an I.V. (intravenous) infusion.

In both parts participants will undergo evaluations of the safety, PK (pharmacokinetics), PD (pharmacodynamics) and anti-tumour efficacy of NUC-3373

Participants may continue to receive NUC-3373 until disease progression or unacceptable toxicity occurs.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 12

Arm	Type	Receives
Part 1 (weekly administration) NUC-3373 125mg/m2	Experimental	Drug: NUC-3373NUC-3373 125mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 250mg/m2	Experimental	Drug: NUC-3373NUC-3373 250mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 500mg/m2	Experimental	Drug: NUC-3373NUC-3373 500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 750mg/m2	Experimental	Drug: NUC-3373NUC-3373 750mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 1125mg/m2	Experimental	Drug: NUC-3373NUC-3373 1125mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 1500mg/m2	Experimental	Drug: NUC-3373NUC-3373 1500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 1875mg/m2	Experimental	Drug: NUC-3373NUC-3373 1875mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 2500mg/m2	Experimental	Drug: NUC-3373NUC-3373 2500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 1 (weekly administration) NUC-3373 3250mg/m2	Experimental	Drug: NUC-3373NUC-3373 3250mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 8, Day 15, Day 22 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 2 (two weekly administration) NUC-3373 1500mg/m2	Experimental	Drug: NUC-3373NUC-3373 1500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 15 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 2 (two weekly administration) NUC-3373 1875mg/m2	Experimental	Drug: NUC-3373NUC-3373 1875mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 15 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.
Part 2 (two weekly administration) NUC-3373 2500mg/m2	Experimental	Drug: NUC-3373NUC-3373 2500mg/m2 solution for injection/infusion IV Infusion on Day 1, Day 15 (28 day cycle). Participants can remain on study and receive treatment until disease progression or unacceptable toxicity occurs.

Who may qualify

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

Key inclusion criteria (12 listed)

Provision of signed written informed consent.
Diagnosis: Histologically confirmed diagnosis of solid tumour, which is not amenable to standard chemotherapy, is refractory to standard chemotherapy or for which no standard chemotherapy exists.
Age ≥ 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
Life expectancy of ≥ 12 weeks.

Key exclusion criteria (22 listed)

History of allergic reactions attributed to previous 5-FU or capecitabine treatment.
History of allergic reactions to any of the components of the diluent solutions supplied with NUC-3373.
Symptomatic CNS or leptomeningeal metastases.
Participants with a history of myocardial infarction within the last 5 years or with significant cardiac arrhythmias requiring medication or pacemaker.
Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy for bone pain), immunotherapy or any other anticancer agent within 28 days of first administration of the IMP.

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	Drug	Part 1 (weekly administration) NUC-3373 1125mg/m2, Part 1 (weekly administration) NUC-3373 125mg/m2, Part 1 (weekly administration) NUC-3373 1500mg/m2, Part 1 (weekly administration) NUC-3373 1875mg/m2, Part 1 (weekly administration) NUC-3373 2500mg/m2, Part 1 (weekly administration) NUC-3373 250mg/m2, Part 1 (weekly administration) NUC-3373 3250mg/m2, Part 1 (weekly administration) NUC-3373 500mg/m2, Part 1 (weekly administration) NUC-3373 750mg/m2, Part 2 (two weekly administration) NUC-3373 1500mg/m2, Part 2 (two weekly administration) NUC-3373 1875mg/m2, Part 2 (two weekly administration) NUC-3373 2500mg/m2

Primary outcome

To establish the recommended Phase 2 Dose (RP2D) of NUC-3373 that will optimise the risk/benefit reward for the participants, administered weekly (Part 1) and when administered fortnightly (Part 2), as a single I.V. infusion.
Time frame: To decide if the next cohort can be opened at a higher dose level, the Trial Management Group (TMG) will review available data (e.g. safety profile) once all participants in the preceding cohort have completed the first cycle through to Day 28.
The RP2D is the most appropriate dose that will optimise the risk/benefit reward for the participants. RP2D determination will take into consideration the plasma PK, PD assessments, the nature of the PK/PD relationship, any efficacy signals or any adverse events observed during the conduct of the dose-escalation and the available non clinical data. The RP2D will be determined by dose escalation with sequential participants receiving increasing doses of NUC-3373 in a standard '3 + 3' cohort design. Dose escalation will stop when the Maximum Tolerated Dose (MTD)/RP2D have been defined for that Part or a decision is made by the Trial Management Group to halt enrolment.

12 secondary outcomes

Dose Limiting Toxicities (DLT) to assess the tolerability of NUC-3373
Time frame: Assessment starts at first IMP administration (Cycle 1 Day 1) until the first cycle completion (Day 28)
Dose Limiting Toxicities (DLT) and SAEs/AEs to assess the safety of NUC-3373
Time frame: Adverse event monitoring starts at IMP administration (Day 1) until 28 days after the final dose of IMP has been administered.
Analysis of NUC-3373 metabolites in plasma to determine Area under the curve (AUC)
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in plasma to determine Peak Plasma Concentration (Cmax)
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in plasma to determine Clearance
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in plasma to determine plasma half T1/2
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC to determine Peak Plasma Concentration (Cmax)
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC to determine Area under the curve (AUC)
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC determine plasma half T1/2
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Analysis of NUC-3373 metabolites in PBMC to determine Clearance
Time frame: PK samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Measuring the ratio between the intracellular dTMP and dUMP concentrations.
Time frame: PD samples will be collected on Cycle 1 Day 1 and Cycle 1 Day 15
Response Evaluation Criteria in Solid Tumours (RECIST) to explore the anti-tumour activity of NUC-3373
Time frame: Tumour assessment (CT scan/MRI scan) will be performed throughout study completion, every 8 weeks, an average of 6 per year.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2024.
Derived from this study: PubMed 38566164Spiliopoulou P, Kazmi F, Aroldi F, Holmes T, Thompson D, Griffiths L, Qi C, Parkes M, Lord S, Veal GJ, Harrison DJ, Coyle VM, Graham J, Jeffry Evans TR, Blagden SP. A phase I open-label, dose-escalation study of NUC-3373, a targeted thymidylate synthase inhibitor, in patients with advanced cancer (NuTide:301). J Exp Clin Cancer Res. 2024 Apr 2;43(1):100. doi: 10.1186/s13046-024-03010-1.
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.

Sarah P Blagden, PhD, FRCP principal investigator

University of Oxford

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NUC-3373 in people with Cancer, run by University of Oxford at 3 sites in United Kingdom.

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 12 inclusion and 22 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 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United Kingdom. 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 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.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

To establish the recommended Phase 2 Dose (RP2D) of NUC-3373 that will optimise the risk/benefit reward for the participants, administered weekly (Part 1) and when administered fortnightly (Part 2), as a single I.V. infusion. (time frame: To decide if the next cohort can be opened at a higher dose level, the Trial Management Group (TMG) will review available data (e.g. safety profile) once all participants in the preceding cohort have completed the first cycle through to Day 28.). 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 NCT02723240, which also lists 1 linked publication.

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 14 Feb 2024.