Absorption, Metabolism, Excretion and Pharmacokinetics of a Single Dose [14C]AZD2014 Followed by a Multiple Dose Phase
Condition: Solid Malignancies
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

Summary: 
      This Phase 1, open label, single centre, non-randomised study in patients with advanced solid
      malignancies consists of two parts:

        1. Single Dose Period - will characterise the absorption, metabolism, excretion and
           pharmacokinetics of a single oral dose of [14C]AZD2014 from the body

        2. Multiple Dose Period - will further assess the safety and tolerability and anti-tumour
           activity of multiple doses of AZD2014 when given as a monotherapy or given in
           combination with paclitaxel or fulvestrant.
    

Detailed description: 
      This is a Phase I, open label, single centre, non-randomised study in patients with advanced
      solid malignancies that is refractory or resistant to standard treatment or where no suitable
      effective standard treatment exists or for whom paclitaxel or fulvestrant are appropriate
      treatment choices. The study will be divided in two parts:

        1. Single Dose Period - will enrol up to 6 evaluable patients to characterise the
           absorption, metabolism, excretion and pharmacokinetics of a single radiolabelled [14C]
           oral dose of 125mg AZD2014 via residential intensive PK sampling over 8 days. An
           evaluable patient is defined as patient who does not vomit within 2 hours post dose and
           who has completed the scheduled PK sampling.

        2. Multiple Dose Period - patients who have completed the Single Dose Period may continue
           to receive treatment as outpatients. Patients will be allocated to different treatment
           regimes as decided between Investigator and patient on a risk / benefit basis. From Day
           1, Cycle 1, non-radiolabelled AZD2014 treatment will be administered as oral tablets to
           patients, either as:

      i. 50mg BD monotherapy ii. 125mg BD taken on first 2 days of treatment each week in
      combination with 500mg intramuscular fulvestrant on Day 1, Cycle 1, Day 15, Cycle 1; Day 1,
      Cycle 2, then Day 1 of each monthly cycle thereafter iii. 50mg BD taken on first 3 days of
      treatment each week for 6 weeks in combination with a single weekly paclitaxel infusion
      (80mg/m2 ) followed by a one week break from treatment where no AZD2014 or paclitaxel will be
      given. This 7 week schedule composes one cycle of treatment. Patients will be given up to 6
      cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed
      appropriate by the Investigator.

      Radiolabelled AZD2014 will be administered to fasted patients (i.e. no food 2 hours before
      and 1 hour after each dose). Non-radiolabelled AZD2014 will be administered either under
      fasted or non-fasted conditions. The safety and tolerability and anti-tumour activity of
      AZD2014 and combination with paclitaxel or fulvestrant will be evaluated in all enrolled
      patients respectively using conventional safety parameters, AEs/SAEs and RECIST 1.1.
    

Intervention name(s): [14C]AZD2014; Multiple dose AZD2014; Fulvestrant; Paclitaxel
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Radiolabelled dual TORC1/TORC2 inhibitor; Dual TORC1/TORC2 inhibitor; Hormonal Agent; Taxane
Intervention MeSH terms: Paclitaxel; Fulvestrant
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Radiolabelled