UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours

Dillon, M; Ellis, S; Grove, L; McLellan, L; Clack, G; Smith, S; Laude, J; ... Harrington, K; + view all (2016) PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours. Presented at: ASCO 2016 Annual Meeting: Poster Session, Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics, Chicago. Green open access

[img]
Preview
Text
Dillon et al A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia.pdf

Download (617kB) | Preview

Abstract

Tumour control rates from radiation therapy (RT) are limited by normal tissue toxicities. Novel strategies are required to selectively sensitize tumour cells to radiation-induced DNA damage. The G2 cell cycle checkpoint is an attractive target for this, as normal cells will be protected by their intact G1 checkpoint, which is lost in the majority of cancer cells. ATR is an important mediator of the G2 checkpoint. Preclinical data suggest that ATR inhibition will sensitise to DNA damaging therapies, including RT. This multi-part phase 1 trial aims to assess safety and tolerability and preliminary anti-tumour activity of the ATR inhibitor AZD6738 as monotherapy and in combination with palliative RT, escalating both drug and radiation dose at a dose-fractionation relevant to radical treatment. The design aims to test a novel agent at the earliest stage of clinical development and assess safety in combination with RT, with the aim of moving to a radically-treated population if tolerated. Methods: Participants have advanced solid tumours without standard systemic therapy options. The trial comprises three parts: parts A and B will assess AZD6738 as a single agent in dose escalation to MTD (part A), followed by expansion cohorts enriched for defective DNA damage response (part B). Part C will assess AZD6738 in combination with palliative RT in which participants will receive 20 Gy in 10 fractions, with per cohort escalation of drug dose to monotherapy MTD if tolerated. At the highest tolerated combination dose, the RT dose will be escalated to 30 Gy in 15 fractions. Maintenance AZD6738 post-RT will be tested at the highest tolerated combination dose. The study opened in August 2014. The study is dose escalating in part A and part C has opened and treated its first patient. Part B will open when dose escalation has completed. PATRIOT is sponsored by The Royal Marsden, funded by the Cancer Research UK/AstraZeneca Combinations Alliance and supported by supply of free drug and distribution costs from Astra Zeneca. Clinical trial information: NCT02223923

Type: Poster
Title: PATRIOT: A phase I study to assess the tolerability, safety and biological effects of a specific ataxia telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours
Event: ASCO 2016 Annual Meeting: Poster Session, Developmental Therapeutics - Clinical Pharmacology and Experimental Therapeutics
Location: Chicago
Dates: 3-7 June 2016
Open access status: An open access version is available from UCL Discovery
Publisher version: http://meetinglibrary.asco.org/content/128919?medi...
Language: English
Additional information: Poster Board Number: Board 297a. Copyright © 2016 American Society of Clinical Oncology
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/1503790
Downloads since deposit
192Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item