PIPA: Combination of PI3 kinase inhibitors and PAlbociclib

• Research type

  Research Study

• Full title

  PIPA: A Phase Ib study to assess the safety, tolerability and activity of the PI3K inhibitors, taselisib (GDC-0032) or pictilisib (GDC-0941), in combination with PAlbociclib, with the subsequent addition of fulvestrant in PIK3CA-mutant breast cancers.

• IRAS ID

  159997

• Contact name

  Nick Turner

• Contact email

  nick.turner@icr.ac.uk

• Sponsor organisation

  The Royal Marsden NHS Foundation Trust

• Eudract number

  2014-002658-37

• Duration of Study in the UK

  2 years, 9 months, 1 days

• Research summary

  Research Summary

  The purpose of this study is to find out the side effects and safety of a combination of two new anti-cancer drugs, palbociclib and either pictilisib (GDC-0941) or taselisib (GDC-0032) and to determine the most appropriate dose of this combination. During Part A cohorts of 3 patients will be treated with escalating doses of the combination of palbociclib and taselisib (Arm 1) or palbociclib and pictilisib (Arm 2). Once Part A has been completed the combination with the optimum safety and pharmacokinetic/pharmacodynamic profile will be taken forward to the Part B. In Part B patients will be recruited to two cohorts; one cohort enrolling patients with ER positive, HER-2 negative breast cancer and one cohort enrolling patients with advanced tumours with mutations that disrupt the PI3K-AKT pathway.

  Lay summary of study results

  At both doses and schedules there was significant (or substantial where statistical analysis could not be performed) decreases in pSer473 AKT when normalised to total AKT and pSer9 GSK3β when normalised to total GSK3β post-dose on C1D15 in PRP. This is proof of mechanism that taselisib is inhibiting PI3K signalling in the patients at the doses tested. There was significant decrease in pSer780 Rb when normalised to total Rb on C1D15 pre-dose in tumour. This is proof of mechanism that palbociclib is inhibiting CDK4/6 in tumour at the doses and schedules tested.
  
  The study was published in Cancer Discovery - see link: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbVSq-2F1dbX8ahKDIJ1xPLHRKA94lph5ROt8sfgriFJaqHeutgVV-2BcWPUyehIyi4rWG2FjDnMrcNOIMTdqDsKXGj-2Bc7AM4e-2FGiCdMkQ6b3qo-2FB4oKDh6LFmW8yf2paI4hXyh6bKJgsCkInscCc22U4rwc-3D6zPX_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YIdBuJmoT3-2BuKFS5vfGTgImpcCLWB2WjF-2FfxUxso3-2FKSDXhRzubouxNwxmWccA1be4HGY6A9S3UPdPCVS6-2B50UZYk4QW0HeNBBrF90FKRSWPtMZd8umZ9Ita66xX0rRfip24CBhMGNkvKBATsaEe4lGf22rl8hEP2OZph6rrVrCkQ-3D-3D&data=05%7C02%7Cchelsea.rec%40hra.nhs.uk%7C6334ff315a97409a2c0d08dc0c4c7cf9%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638398769852839049%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=rH8%2B0x540qoWFWDN5V5kNBSyNeEz8KyqVHZgvxiZthc%3D&reserved=0

• REC name

  London - Chelsea Research Ethics Committee

• REC reference

  14/LO/1981

• Date of REC Opinion

  5 Jan 2015

• REC opinion

  Further Information Favourable Opinion