AZD8186 First Time In Patient Ascending Dose Study
Condition: Advanced Castrate-resistant Prostate Cancer CRPC; Squamous Non-Small Cell Lung Cancer sqNSCLC; Triple Negative Breast Cancer TNBC
MeSH terms: Breast Neoplasms; Lung Neoplasms; Prostatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Part A: AZD8186 monotherapy; Part B: AZD8186 monotherapy; Part C1: Abiraterone acetate combination with AZD8186; Part D1: AZD2014 combination with AZD8186; Part D2 AZD2014 combination with AZD8186; Part C2: Abiraterone acetate combination with AZD8186
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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.; Part B will be at a dose(s) and schedule(s) at or below from Part A; Dose and schedule finding of AZD8186 added to approved labelled dose of abiraterone acetate (with prednisone).; Dose & schedule finding of AZD8186 in combination with AZD2014; Combination AZD8186/ AZD2014 dose expansion at dose determined in Part D1; Dose expansion of AZD8186 at dose determined in Part C1 added to approved dose of abiraterone acetate (with prednisone)
Intervention MeSH terms: Abiraterone Acetate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Advanced Castrate-resistant Prostate Cancer(CRPC); Squamous Non-Small Cell Lung Cancer(sqNSCLC); Triple Negative Breast Cancer(TNBC); PTEN-deficient/mutated Advanced Solid Malignancies; PIK3CB mutated/amplified advanced solid malignancies