A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleoside Analogue, in Patients With Advanced Solid Tumours.
This is a two-part, Phase I, open label study of NUC-1031 as a single agent, administered IV
weekly on days 1, 8, & 15 (Schedule A) or twice weekly on days 1 & 5, 8 & 12, 15 &19
(Schedule B) of a 28 day- cycle regimen. An initial dose-escalation phase (Part I) will be
followed by an expansion cohort phase (Part II) using the preferred regimen from Part 1. In
Part I, sequential patients will be assigned to increasing doses of NUC-1031 in a standard
'3 + 3' design to determine the recommended Phase II dose (RP2D). There will be a mandatory
review of all available data (in particular the safety profile and preliminary PK data
through to at least the last scheduled day of Cycle 1) following enrolment of the second
cohort of both schedule A and B to select the preferred administration schedule to take
forward for ongoing evaluation. Subsequently, safety review will be conducted prior to
enrolment of new subjects after every 2 planned dose levels and prior to definition of RP2D.
In Part II (dose expansion) additional patients will be enrolled to receive NUC-1031 at the
RP2D and dosing frequency determined from Part I of the study. To be eligible to enter Part
II, patients must have a diagnosis of cancer of the pancreas, ovary, lung (NSCL), breast, or
bladder. During Part II, further information will be obtained regarding safety, PK, PD and
preliminary anti-tumour efficacy of NUC-1031 at RP2D.
In both parts of the study, patients may continue to receive NUC-1031 for up to 6 cycles or
until disease progression, the occurrence of unmanageable drug related toxicity despite dose
modification or if the study participant declines further treatment.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine the RP2D of NUC-1031 administered as either an I.V. weekly or twice-weekly schedule in patients with advanced solid tumours.
Adverse events (AE) and changes from baseline in vital signs, clinical laboratory parameters, and electrocardiography (ECG) assessments will be assessed
Dr Blagden, PhD FRCP
Imperial College London
United Kingdom: Medicines and Healthcare Products Regulatory Agency