Title

NuTide:301

Chief Investigator: 

Study Design

The study is split into two phases, the dose escalation Phase and the Dose Expansion Phase.

The dose escalation has 2 parts: Part 1 is to assess the safety and tolerability of NUC-3373 administered weekly as an I.V. infusion on day 1, 8, 15, 22 of a 28-day cycle. Part 2 is assess the safety and tolerability of NUC-3373 administered fortnightly as an I.V. infusion on day 1, 15, of a 28-day cycle

The dose Expansion phase is to obtain a preliminary estimate of anti-tumor activity in specific tumour types as measured by response rate and duration of response and to further assess the safety profile of NUC-3373 administered over multiple cycles at the RP2D.

Study Population: Males or females with a histologically confirmed diagnosis of any solid tumour not amenable to standard therapy, refractory to standard therapy or for which no standard therapy exists will be eligible to enter the study provided they fulfil eligibility criteria.

Study Schema:

 

Study Status: Open

Target Recruitment: ~18 in each part + ~20 in each cohort expansion phase.

Current Recruitment: Open to recruitment

Recruiting Sites:

  • Churchill Hospital - Oxford University Hospitals NHS Trust.
  • Beatson, West of Scotland Cancer Centre.
  • Further sites may be opened.

Inclusion Criteria:

1. Provision of signed written informed consent.

2. 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.

3. Age ≥ 18 years.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

5. Life expectancy of ≥ 12 weeks.

6. 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).

7. 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.

8. Adequate liver function, as determined by: Serum total bilirubin ≤1.5 x ULN, AST and ALT ≤ 2.5 x ULN.

9. 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.

10. Left Ventricular Ejection Fraction (LVEF) ≥50% on echocardiogram.

11. Ability to comply with protocol requirements.

12. Female participants of childbearing potential must have a negative serum pregnancy test at screening and at Cycle 1 Day 1 prior to the first scheduled IMP administration.

 

Exclusion Criteria:

1. History of allergic reactions attributed to previous 5-FU or capecitabine treatment.

2. History of allergic reactions to any of the components of the Companion Infusion Solutions supplied with NUC-3373 (see Section 10.2).

3. Symptomatic CNS or leptomeningeal metastases.

4. Participants with a history of myocardial infarction within the last 5 years or with significant cardiac arrhythmias requiring medication or pacemaker.

5. History of a cardiac event attributed to previous 5-FU / capecitabine treatment.

6. 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.

  • For hormone or biological therapy within 14 days of first administration of IMP.

7. 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.

8. Another active cancer excluding basal cell carcinoma or intraepithelial neoplasia (CIN/cervical in situ or melanoma in situ).

9. 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.

10. 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.

11. Known HIV or known active Hepatitis B or C.

12. 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.

13. 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. Sexual abstinence.

14. Participants who are currently breastfeeding.

Primary Objective:  To establish the recommended phase 2 dose of NUC 3373.

Key Dates:

January 2016 -  Opened to recruitment  

July 2017 – Expected study end date

 

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