NCT01884285

AZD8186 First Time In Patient Ascending Dose Study

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 147 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

Summary

This is a phase I, open-label, multicentre study of AZD8186 administered orally in patients with advanced castrate-resistant prostate cancer (CRPC), squamous non-small cell lung cancer (sqNSCLC), triple negative breast cancer (TNBC) and known PTEN-deficient/mutated or PIK3CB mutated/amplified advanced solid malignancies as monotherapy and in combination with abiraterone acetate or AZD2014.

Detailed description

This is a phase I, open-label, multicentre study of AZD8186 administered orally in patients with advanced castrate-resistant prostate cancer (CRPC), squamous non-small cell lung cancer (sqNSCLC), triple negative breast cancer (TNBC) and known PTEN-deficient/mutated or PIK3CB mutated/amplified advanced solid malignancies. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of the patients. There are 4 parts to this study: Part A, monotherapy dose escalation, Part B, monotherapy expansion cohort(s) in PTEN deficient patients at the monotherapy intended therapeutic dose(s) and schedule(s), Part C, AZD8186 added to abiraterone accetate (with prednisone) treatment - dose/ schedule finding followed by expansion phase in PTEN-deficient/mutated or PIK3CB mutated mCRPC and Part D, AZD8186 in combination with AZD2014 (a novel dual mTORC1/2 inibitor) dose/schedule finding followed by expansion phase in PTEN-deficient/mutated or PIK3CB mutated TNBC.

Conditions

• Advanced Castrate-resistant Prostate Cancer CRPC
• Squamous Non-Small Cell Lung Cancer sqNSCLC
• Triple Negative Breast Cancer TNBC

Interventions

Type	Name	Description
DRUG	Part A: AZD8186 monotherapy	The initial schedule will use intermittent dosing of AZD8186. Dose, frequency and schedule in subsequent cohorts may be modified in response to safety, tolerability, pharmacokinetic and preclinical data.
DRUG	Part B: AZD8186 monotherapy	Part B will be at a dose(s) and schedule(s) at or below from Part A
DRUG	Part C1: Abiraterone acetate combination with AZD8186	Dose and schedule finding of AZD8186 added to approved labelled dose of abiraterone acetate (with prednisone).
DRUG	Part D1: AZD2014 combination with AZD8186	Dose \& schedule finding of AZD8186 in combination with AZD2014
DRUG	Part D2 AZD2014 combination with AZD8186	Combination AZD8186/ AZD2014 dose expansion at dose determined in Part D1
DRUG	Part C2: Abiraterone acetate combination with AZD8186	Dose expansion of AZD8186 at dose determined in Part C1 added to approved dose of abiraterone acetate (with prednisone)

Timeline

• Start date: 2013-07-09
• Primary completion: 2019-03-31
• Completion: 2020-02-07
• First posted: 2013-06-24
• Last updated: 2020-05-29

Locations

13 sites across 4 countries: United States, Canada, Spain, United Kingdom