Clinical trial NCT02640755
Conditions: Solid Malignancies
Keywords: Radiolabelled
Sponsor: AstraZeneca
Start date: 2016-01-28; Completion date: 2017-07-06
Enrollment: 4 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Arm will be comprised of \[14C\]AZD2014 followed by AZD2014 Monotherapy arm 2: Arm will be comprised of \[14C\]AZD2014 followed by AZD2014 + Fulvestrant arm 3: Arm will be comprised of \[14C\]AZD2014 followed by AZD2014 + Paclitaxel
Interventions: intervention 1: [14C]AZD2014 intervention 2: Multiple dose AZD2014 intervention 3: Fulvestrant intervention 4: Paclitaxel
Intervention descriptions: intervention 1: Radiolabelled dual TORC1/TORC2 inhibitor intervention 2: Dual TORC1/TORC2 inhibitor intervention 3: Hormonal Agent intervention 4: Taxane

Protocol documents: