NUC-1031 in Patients With Advanced Solid Tumours — ProGem1  

Cancer Clinical Trial

Official title: A Two-part, Phase I Open Label Dose-escalation Study to Assess the Safety, Pharmacokinetics and Clinical Activity of NUC-1031, a Nucleotide Analogue, in Patients With Advanced Solid Tumours.

Status Completed

Clinical Trial Summary

This is a two-part Phase I, open label, dose-escalation, study of NUC-1031 as a single agent in patients with advanced solid tumours who have failed to respond to or who have relapsed after treatment with standard therapy. NUC-1031 is a ProTide of gemcitabine, a drug that has been used widely and effectively against cancers for many years. Both NUC-1031 and gemcitabine work by preventing cancer cells from dividing by attacking their DNA (deoxyribonucleic acid). Non clinical studies have shown that NUC-1031 is more effective than gemcitabine because it is able to reach cancer cells by passive diffusion, is less easily degraded by the cancer cell, and delivers the monophosphate form of the active agent. The first part of the study is to determine recommended phase 2 dose by dose escalation and the second part is to explore preliminary anti-tumour activity.

Clinical Trial Description

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 I. 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 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.

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. 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, until disease progression, for as long as the participant receives clinical benefit in the opinion of the CI, the occurrence of unmanageable drug related toxicity despite dose modification or if the study participant declines further treatment. ;

Related Conditions & MeSH terms

• Cancer

• NCT number: NCT01621854
• Study type: Interventional
• Source: Imperial College London
• Status: Completed
• Phase: Phase 1
• Start date: October 2012
• Completion date: June 2015