Table 4. Ongoing clinical trials of NET plus PI3K/AKT/mTOR inhibitors or (CDK) 4/6 inhibitors.
| Register number (N) | Design | Arms and regimen | Duration | Primary outcome |
|---|---|---|---|---|
| PI3K inhibitor | ||||
|
NCT02273973 N = 330 |
Phase II randomised, double-blind, placebo-controlled trial Randomisation 1:1 |
Arm A: Taselisib (6 mg: 5 days on, 2 off) plus letrozole Arm B: Placebo + letrozole |
16 w | pCR |
|
NCT01923168 N = 360 |
Phase II randomised, double-blind, placebo-controlled trial Randomisation 1:1:1 |
Arm A: BYL719 (300 mg q.d.) + letrozole Arm B: Buparlisib (100 mg q.d.) + letrozole Arm C: Placebo + letrozole |
24 w | pCR |
| AKT inhibitor | ||||
|
NCT01776008 N = 87 |
Phase II, open label, single-arm trial | MK-2206 (q.d. on days 2, 9, 16 and 23) + anastrozole; goserelin acetate on day one of each cycle (if premenopausal) | Maximum four cycles of 28 days each | pCR based on Ki67 values |
| CDK4/6 inhibitor | ||||
|
NCT01723774 N = 29 |
Phase II, open label, single-arm trial | PD0332991 (on days 1–21 of each 28 day cycle) + anastrozole + goserelin acetate on day 1 of each cycle (premenopausal patients only | Maximum four cycles of 28 days each | Complete cell cycle arrest based on Ki67 values |
| NCT0229801 N = 306 |
Phase II randomised, open label Randomisation 3:2:2:2 |
Arm A: Letrozole (14 w) Arm B: Letrozole (2 w) then letrozole + palbociclib* (12 w) Arm C: Palbociclib* (2 w) then letrozole + palbociclib* (12 w) Arm D: Letrozole + palbociclib* (14 w) |
14 w | Change in Ki67 values cCR |
|
NCT02400567 N = 132 |
Phase II randomised, open label Randomisation 1:1 |
Arm A: Chemotherapy (three cycles of FEC100 then three cycles of docetaxel 100 mg/m2) Arm B: Letrozole + palbociclib* (12 w) |
18 w | RCB 0–I index rate |
*
Palbociclib dose – 25 mg capsule orally daily for a three weeks on and one week off cycle, BC – breast cancer, cCR – clinical complete response, CDK – cyclin-dependent kinase, ECOG-PS – Eastern Cooperative Oncology Group performance status, FE –5-fluorouracile 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2), HR – hormonal receptor, ORR – objective response rate, pCR – pathological complete response; RCB – residual cancer burden, w – weeks.