Phase I, AZD8186 in Patients with CRPC, sqNSCLC, TNBc, PTEN malignancy
Research type
Research Study
Full title
A Phase I, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti-tumour Activity of AZD8186 in Patients with Advanced Castration-resistant Prostate Cancer (CRPC), Squamous Non-Small Cell Lung Cancer (sqNSCLC), Triple Negative Breast Cancer (TNBC) and Patients with Known PTEN-deficient/mutated or PIK3CB mutated/amplified Advanced Solid Malignancies, as Monotherapy and in Combination with Abiraterone Acetate or AZD2014
IRAS ID
129536
Contact name
Johann de Bono
Contact email
Sponsor organisation
Astra Zeneca AB
Eudract number
2013-000703-17
Duration of Study in the UK
1 years, 8 months, 30 days
Research summary
This is a first-time-in-patient (FTIP), multicentre trial run in Canada, the USA and the UK which will enroll approximately 60 patients in the study as a whole. There are two parts to this study. In Part A (dose escalation phase) AZD8186 will be administered to advanced castrate-resistant prostate cancer (CRPC), squamous non-small cell lung cancer (sqNSCLC) and triple negative breast cancer (TNBC) patients. Patients with other advanced solid malignancies will also be included if those tumours have been previously molecularly characterised as PTEN deficient; enrollment of patients with other malignancies may be capped (maximum of 2 in the first two cohorts, 1 in subsequent cohorts) to permit adequate enrollment of CRPC, sqNSCLC and TNBC patients. The starting dose of 30 mg is based upon international guidance for starting dose selection for agents in cancer patients (ICHS9)
which recommends that a starting clinical dose for the ‘first-in-human’ study be 1/6th of the non-severely toxic dose (NSTD) observed in non-rodent toxicity studies which was 5 mg/kg twice-daily dosing (BD) in dogs, the most sensitive species. Although animals were dosed continuously in the toxicology experiments, intermittent schedules (including a 5 day on and 2 day off schedule) were found to be as efficacious as continuous dosing in preclinical xenograft models. The starting schedule in this study will use intermittent dosing (5 days of BD dosing,
followed by 2 days off treatment).REC name
South Central - Oxford A Research Ethics Committee
REC reference
13/SC/0374
Date of REC Opinion
18 Oct 2013
REC opinion
Further Information Favourable Opinion