NuTide:701

This is a research study to test a new investigational drug called NUC-7738. NUC-7738 belongs to a new class of anti-cancer agents called ProTides that are specifically designed to transform some of the most widely prescribed chemotherapy agents, nucleoside analogues, into more effective and safer medicines.

The primary objective of this study is to investigate the safety and tolerability of NUC-7738 in subjects with solid tumours or lymphomas. This is a first-in-man study.

The study is funded by NuCANA plc, an Edinburgh based company. Subjects who have solid tumours or lymphomas will be recruited from 3 hospitals in the UK. These subjects will receive the investigational drug in small groups at escalating doses in order to find the safest dose tolerated.

The study will last for around 2 years and subjects will be in the study for approx. 7 months. 

1. Provision of signed written informed consent.

2. Histologically confirmed diagnosis of an advanced solid tumour (Part 1 and 2) or lymphoma (Part 2 only), which is not amenable to standard chemotherapy, is refractory to standard chemotherapy or for which no standard chemotherapy exists.

3. Age ≥ 18 years (no upper age limit).

4. Eastern Cooperative Oncology Group performance status of 0 or 1.

5. Life expectancy of ≥ 12 weeks.

6. Part 1 and Part 2; enrolment of patients with advanced solid tumours. Patients must have measurable disease as per RECIST v1.1 criteria and/or evaluable disease (evaluable: cytologically or radiologically detectable disease such as ascites, peritoneal deposits, or lesions, which do not fulfil RECIST v 1.1 criteria for measurable disease) for solid tumours.

7. Part 2; enrolment of patients with lymphoma. Patients must have bi dimensionally measureable disease as per Cheson et al, 2007 criteria for lymphoma.

8. Adequate bone marrow function as defined by: white blood cell count ≥ 2 × 109/L, absolute neutrophil count ≥ 1.5 × 109/L, platelet count ≥ 90 × 109/L, and haemoglobin ≥ 100 g/L.

9. Adequate liver function, as determined by: serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN or ≤ 5.0 × ULN with metastatic liver disease.

10. Adequate renal function as determined by: serum creatinine within ≤ 1.5 × ULN or calculated creatinine clearane ≥ 50 mL/min/1.73 m2 (using Cockcroft-Gault equation).

11. Ability to comply with protocol requirements.

12. Female patients of child-bearing potential must have a negative serum pregnancy test within 3 days prior to the first NUC-7738 administration. All 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 of contraception, from the time of screening until 30 days after the last dose of study medication.

13. Willing to undergo biopsy of suitably accessible lesions. Patients who do not have easily accessible tumour for biopsy should not be put at undue risk for sample collection and these patients remain eligible for the study. 

1. History of allergic reactions to any of the components of NUC-7738.

2. Central nervous system or leptomeningeal metastases.

3. Chemotherapy, radiotherapy (other than a short cycle of palliative radiotherapy for bone pain), immunotherapy, or exposure to another investigational agent within 28 days of first administration of the Investigational Medicinal Product:

a. For nitrosoureas and mitomycin C within 6 weeks of first administration of NUC-7738.

b. For hormone or biological therapy within 14 days of first administration of NUC-7738.

c. Corticosteroid treatment is allowed during the screening period but should be weaned to a dose of 10 mg prednisolone (or steroids equivalent) by Cycle 1 Day 1.

4. Prior toxicities from anti-cancer agents or radiotherapy, which have not regressed to Grade ≤ 1 severity (NCI-CTCAE version 5.0), excluding neuropathy and alopecia.

5. Presence of any uncontrolled concomitant illness, serious illnesses, medical conditions, 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, including the following:

a. Congestive heart failure (New York Heart Association Class III or Class IV).

b. Myocardial infarction within 6 months of the first dose of study medication.

c. Unstable or poorly controlled angina pectoris.

d. Complete left bundle branch, bifascicular block or other clinically significant abnormal ECG finding.

e. A history of or current risk factor for Torsades de Point (e.g., heart failure, hypokalemia, or a family history of long QT syndrome).

f. A history of, or current diagnosis of, interstitial pneumonitis or pulmonary fibrosis.

6. Known Human Immunodeficiency Virus positive or known active hepatitis B or C. Presence of an active bacterial or viral infection including Herpes Zoster or chicken pox.

7. Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the Investigator, may affect the patient’s ability to sign the informed consent and undergo study procedures.

8. Currently pregnant, lactating or breastfeeding.

9. QTc interval > 450 milliseconds for males and > 470 milliseconds for females.

10. Concomitant use of drugs known to prolong QT/QTc interval.

11. Have received a live vaccination within four weeks of first planned dose of study medication. 

Research Nurse: Sirjana Subedi (x3921) Sirjana.Devkota@lthtr.nhs.uk

Administrator: Zahir Shah (x8475)