NCT02389842: PIPA

PIPA: Combination of PI3 Kinase Inhibitors and PAlbociclib

Completed Phase 1 Last updated 26 September 2024

What this trial tests

Phase 1 trial testing Palbociclib + Taselisib / Pictilisib in Advanced Solid Tumours in 79 participants. Completed in 26 May 2021.

Timeline

25 March 2015

Primary endpoint
31 October 2018

26 May 2021

Quick facts

Lead sponsor	Royal Marsden NHS Foundation Trust
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	79
Start date	25 March 2015
Primary completion	31 October 2018
Estimated completion	26 May 2021
Sites	2 locations across United Kingdom

Drugs / interventions tested

• Palbociclib + Taselisib / Pictilisib (palbociclib-taselisib-pictilisib) — full drug profile →

Conditions studied

• Advanced Solid Tumours — all drugs for Advanced Solid Tumours →
• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Royal Marsden NHS Foundation Trust

Who can join

18 and older, any sex, with Advanced Solid Tumours or Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Part A: This is a phase Ib trial combining the CDK4/6 inhibitor palbociclib with the PI3K inhibitors taselisib, or pictilisib. There are two treatment arms during the dose escalation phase where patients will receive either taselisib OR pictilisib in combination with palbociclib. Palbociclib, taselisib and pictilisib can all be given orally once daily with food, in a 21-days-on and 7-days-off schedule. Once the MTD is reached, the combination with the optimum safety and PK/PD profile will be taken forward to the dose expansion phase (Part B).

Part B1: At the MTD dose expansion, fulvestrant will be administered in addition to palbociclib and taselisib or pictilisib orally once daily, in a 21-days-on and 7-days-off schedule in the ER+ve HER2-ve PIK3CA mutant breast cancer cohort. Fulvestrant will be given intramuscularly on Day 1, Day 15 in cycle one followed by Day 1 for all subsequent cycles.

Part B2: At the MTD dose expansion, patients with PIK3CA mutant advanced solid tumours will be treated with palbociclib and taselisib or pictilisib orally once daily, in a 21-days-on and 7-days-off schedule.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Insights into Molecular Classifications of Triple-Negative Breast Cancer: Improving Patient Selection for Treatment.
   Garrido-Castro AC, Lin NU, Polyak K. · · 2019 · cited 1061× · PMID 30679171 · DOI 10.1158/2159-8290.cd-18-1177
2. Role of PI3K/AKT pathway in cancer: the framework of malignant behavior.
   Jiang N, Dai Q, Su X, Fu J, et al · · 2020 · cited 419× · PMID 32333246 · DOI 10.1007/s11033-020-05435-1
3. CDK4 and CDK6 kinases: From basic science to cancer therapy.
   Fassl A, Geng Y, Sicinski P. · · 2022 · cited 351× · PMID 35025636 · DOI 10.1126/science.abc1495
4. Activation of PI3K/AKT/mTOR Pathway Causes Drug Resistance in Breast Cancer.
   Dong C, Wu J, Chen Y, Nie J, et al · · 2021 · cited 260× · PMID 33790792 · DOI 10.3389/fphar.2021.628690
5. Single-Cell Dynamics Determines Response to CDK4/6 Inhibition in Triple-Negative Breast Cancer.
   Asghar US, Barr AR, Cutts R, Beaney M, et al · · 2017 · cited 219× · PMID 28606920 · DOI 10.1158/1078-0432.ccr-17-0369
6. The Strange Case of CDK4/6 Inhibitors: Mechanisms, Resistance, and Combination Strategies.
   Knudsen ES, Witkiewicz AK. · · 2017 · cited 218× · PMID 28303264 · DOI 10.1016/j.trecan.2016.11.006
7. PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.
   Mishra R, Patel H, Alanazi S, Kilroy MK, et al · · 2021 · cited 207× · PMID 33801659 · DOI 10.3390/ijms22073464
8. Targeted therapy in cancer.
   Tsimberidou AM. · · 2015 · cited 156× · PMID 26391154 · DOI 10.1007/s00280-015-2861-1