NCT04318223

Palbociclib Plus Fulvestrant in Women With Hormone Receptor Positive and Human Epidermal Growth Factor Receptor Type 2 Negative Locally Advanced or Metastatic Breast Cancer Previously Treated With a CDK4/6 Inhibitor in Combination With Hormonal Therapy

Status unknown Phase 2 Last updated 23 March 2020

What this trial tests

Phase 2 trial testing Palbociclib in Metastatic Breast Cancer in 168 participants. Status unknown.

Timeline

16 July 2019

Primary endpoint
31 July 2023

31 July 2023

Quick facts

Lead sponsor	Consorzio Oncotech
Phase	Phase 2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	168
Start date	16 July 2019
Primary completion	31 July 2023
Estimated completion	31 July 2023
Sites	19 locations across Italy

Drugs / interventions tested

• Palbociclib (Palbociclib) — full drug profile →

Conditions studied

• Metastatic Breast Cancer — all drugs for Metastatic Breast Cancer →
• Locally Advanced Breast Cancer — all drugs for Locally Advanced Breast Cancer →

Sponsor

Consorzio Oncotech — full company profile →

Who can join

Adults 18 to 64, female only, with Metastatic Breast Cancer or Locally Advanced Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

The aim of the present study is to evaluate the efficacy and safety of palbociclib plus fulvestrant after failure of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) plus a CDK4/6 inhibitor, in women with HR+ and HER2- LABC or MBC.

Primary endpoint:

1. To assess the clinical benefit rate (CBR) of the combination treatment palbociclib plus fulvestrant at progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and a CDK4/6 inhibitor.

Clinical benefit rate for primary efficacy endpoints derivation will be based on the local (treating center's) radiologist's/investigator's tumor assessment.
* For patients with measurable disease at baseline, progression will be determined according to the RECIST criteria v1.1.
* In the absence of measurable disease at baseline, patients with bone only lesions, lytic or mixed (lytic + sclerotic), will be allowed to enter the study and the following will be considered disease progression among these patients:
* The appearance of one or more new lytic lesions in bone,
* The appearance of one or more new lesions outside of bone,
* Unequivocal progression of existing bone lesions.

Note: Pathologic fracture, new compression fracture, or complications of bone metastases will not be considered as evidence of disease progression, unless one of the above-mentioned criteria is fulfilled.
2. To assess the Quality of Life (QoL) of patients receiving the combination treatment palbociclib plus fulvestrant at progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and a CDK4/6 inhibitor.

Secondary Endpoints:

1. To evaluate the efficacy of the combination of fulvestrant plus palbociclib at the progression of a combined treatment of hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa) and CDK4/6 inhibitors with respect to:

* Overall response rate (ORR)
* Progression Free Survival (PFS)
* Overall Survival (OS)
* Safety and tolerability
2. To assess predictive biomarkers of response/resistance to fulvestrant plus palbociclib using metastatic tumor tissue samples and liquid biopsies.

This study will be performed in pre- and post-menopausal women with HR+/HER2- LABC or MBC whose disease is progressing to a CDK4/6 inhibitor in combination with hormonal therapy (aromatase inhibitor or tamoxifen ± LHRHa).

Patients enrolled will receive study medication until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever comes first.

Publications & conference data

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

1. Epigenetic mechanisms in breast cancer therapy and resistance.
   Garcia-Martinez L, Zhang Y, Nakata Y, Chan HL, et al · · 2021 · cited 319× · PMID 33741974 · DOI 10.1038/s41467-021-22024-3
2. Breast Cancer Treatments: Updates and New Challenges.
   Burguin A, Diorio C, Durocher F. · · 2021 · cited 297× · PMID 34442452 · DOI 10.3390/jpm11080808
3. Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.
   Kaboli PJ, Imani S, Jomhori M, Ling KH. · · 2021 · cited 51× · PMID 34765318
4. Functionalized Nanoparticles Targeting Tumor-Associated Macrophages as Cancer Therapy.
   He Y, de Araújo Júnior RF, Cruz LJ, Eich C. · · 2021 · cited 48× · PMID 34683963 · DOI 10.3390/pharmaceutics13101670
5. Systemic Therapies Following Progression on First-line CDK4/6-inhibitor Treatment: Analysis of Real-world Data.
   Martin JM, Handorf EA, Montero AJ, Goldstein LJ. · · 2022 · cited 43× · PMID 35552450 · DOI 10.1093/oncolo/oyac075
6. Filling the Gap after CDK4/6 Inhibitors: Novel Endocrine and Biologic Treatment Options for Metastatic Hormone Receptor Positive Breast Cancer.
   Mittal A, Molto Valiente C, Tamimi F, Schlam I, et al · · 2023 · cited 32× · PMID 37046675 · DOI 10.3390/cancers15072015
7. The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.
   Gomes I, Abreu C, Costa L, Casimiro S. · · 2023 · cited 12× · PMID 37835528 · DOI 10.3390/cancers15194835
8. Advances in Therapy for Hormone Receptor (HR)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced Breast Cancer Patients Who Have Experienced Progression After Treatment with CDK4/6 Inhibitors.
   Li C, Li X. · · 2021 · cited 8× · PMID 33976551 · DOI 10.2147/ott.s298720