NCT01857193

Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer

Completed Phase 1 Last updated 13 April 2021

What this trial tests

Phase 1 trial testing ribociclib (LEE011) in Breast Cancer in 132 participants. Completed in 16 April 2020.

Timeline

6 September 2013

Primary endpoint
14 March 2018

16 April 2020

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	132
Start date	6 September 2013
Primary completion	14 March 2018
Estimated completion	16 April 2020
Sites	13 locations across France, Hong Kong, Belgium, United States, Spain

Drugs / interventions tested

• ribociclib (LEE011) — full drug profile →
• Exemestane (exemestane) — full drug profile →
• Everolimus (RAD001) — full drug profile →

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Dose Escalation part of the study: To estimate the MTD(s) and/ or RP2D of LEE011 in combination with everolimus + exemestane, and LEE011 in combination with exemestane, and to characterize the safety and tolerability of the combinations of everolimus + exemestane + LEE011 and LEE011 + exemestane in patients with ER+ HER2- advanced breast cancer

Dose Expansion part of the study: To characterize the safety and tolerability of the triplet combination of LEE011 + everolimus + exemestane in patients naïve or refractory to CDK4/6 inhibitor based therapy, and the safety and tolerability of the doublet combination of LEE011 + exemestane in patients refractory to CDK4/6 inhibitor based therapy (except patients treated with prior LEE011 are not allowed in Group 3).

Publications & conference data

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

1. The history and future of targeting cyclin-dependent kinases in cancer therapy.
   Asghar U, Witkiewicz AK, Turner NC, Knudsen ES. · · 2015 · cited 1349× · PMID 25633797 · DOI 10.1038/nrd4504
2. Cyclin D1, cancer progression, and opportunities in cancer treatment.
   Qie S, Diehl JA. · · 2016 · cited 527× · PMID 27695879 · DOI 10.1007/s00109-016-1475-3
3. The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer.
   Ding L, Cao J, Lin W, Chen H, et al · · 2020 · cited 385× · PMID 32183020 · DOI 10.3390/ijms21061960
4. CDK4/6 Inhibitors: The Mechanism of Action May Not Be as Simple as Once Thought.
   Klein ME, Kovatcheva M, Davis LE, Tap WD, et al · · 2018 · cited 308× · PMID 29731395 · DOI 10.1016/j.ccell.2018.03.023
5. 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
6. Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers.
   Finn RS, Aleshin A, Slamon DJ. · · 2016 · cited 254× · PMID 26857361 · DOI 10.1186/s13058-015-0661-5
7. 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
8. CDK4/6 inhibition in breast cancer: current practice and future directions.
   Pernas S, Tolaney SM, Winer EP, Goel S. · · 2018 · cited 212× · PMID 30038670 · DOI 10.1177/1758835918786451