NCT02871791

A Phase 1b/2a Study Of Palbociclib In Combination With Everolimus And Exemestane In Postmenopausal Women With Estrogen Receptor Positive and HER2 Negative Metastatic Breast Cancer

Completed Phase 1/Phase 2 Results posted Last updated 2 August 2022

What this trial tests

Phase 1/Phase 2 trial testing Palbociclib in Human Epidermal Growth Factor 2 Negative Carcinoma of Breast in 41 participants. Completed in 1 September 2021.

Timeline

24 August 2016

Primary endpoint
3 December 2020

1 September 2021

Quick facts

Lead sponsor	Dana-Farber Cancer Institute
Phase	Phase 1/Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	41
Start date	24 August 2016
Primary completion	3 December 2020
Estimated completion	1 September 2021
Sites	1 location across United States

Drugs / interventions tested

• Palbociclib (Palbociclib) — full drug profile →
• Everolimus (everolimus) — full drug profile →
• Exemestane (exemestane) — full drug profile →

Conditions studied

• Human Epidermal Growth Factor 2 Negative Carcinoma of Breast — all drugs for Human Epidermal Growth Factor 2 Negative Carcinoma of Breast →
• Hormone Receptor (HR)-Positive Breast Cancer — all drugs for Hormone Receptor (HR)-Positive Breast Cancer →

Sponsor

Dana-Farber Cancer Institute

Who can join

18 and older, any sex, with Human Epidermal Growth Factor 2 Negative Carcinoma of Breast or Hormone Receptor (HR)-Positive Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Clinical Benefit Rate (CBR) [Phase 2a]
  Time frame: Disease evaluations were performed every 8 weeks (within 24 weeks of initiation of study treatment) or every 12 weeks (greater than 24 weeks of initiation of study treatment). Treatment duration has a median of 111 days and maximum of 681 days.
  CBR is defined as the proportion of participants achieving complete response, partial response or stable disease for more than 6 months (CR+PR+SD ≥ 24 weeks) taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.

Sponsor's own description

This research study is studying a combination of targeted therapy and hormonal therapy as a possible treatment for breast cancer that has spread to other places in the body and is hormone receptor positive (HR+) and HER2-negative.

The names of the study interventions involved in this study are:

* Palbociclib
* Everolimus
* Exemestane

Publications & conference data

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

1. 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
2. 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
3. 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
4. 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
5. Endocrine Resistance in Hormone Receptor Positive Breast Cancer-From Mechanism to Therapy.
   Rani A, Rani A, Stebbing J, Giamas G, et al · · 2019 · cited 162× · PMID 31178825 · DOI 10.3389/fendo.2019.00245
6. Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases.
   Shah N, Mohammad AS, Saralkar P, Sprowls SA, et al · · 2018 · cited 102× · PMID 29604436 · DOI 10.1016/j.phrs.2018.03.021
7. CDK4/6 Inhibitors: Game Changers in the Management of Hormone Receptor–Positive Advanced Breast Cancer?
   Shah M, Nunes MR, Stearns V. · · 2018 · cited 96× · PMID 29847850
8. Endocrine-Resistant Breast Cancer: Mechanisms and Treatment.
   Hartkopf AD, Grischke EM, Brucker SY. · · 2020 · cited 78× · PMID 32982644 · DOI 10.1159/000508675