Neoadjuvant Biomarker ResearcH Study of Palbociclib Combined With Endocrine Therapy in Estrogen Receptor Positive/HER2 Negative Breast CAncer (NeoRHEA)

NCT03065621 | Completed Phase 2

• 1 other identifier: IJB-BC-NEORHEA-2016
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

This is an open-label, single arm, phase 2 trial that will include pre or post-menopausal female subjects, that have ER-positive, HER2-negative early breast cancer. Subject will receive 4 cycles of palbociclib 125 mg (each cycle of palbociclib consists of treatment from D1 to D21 followed by a week of rest) combined with endocrine therapy given continuously (each cycle of endocrine therapy consists of treatment from D1 to D28). The endocrine therapy will be determined according to the menopausal status of the subject evaluated at the study screening.

Conditions

Breast Cancer Female

Keywords

Breast

Outcome Measures

Primary Outcomes (1)

• To identify biomarkers of resistance to a 4-month preoperative treatment of palbociclib plus endocrine therapy defined as stable or progressive disease by ultrasound (based on WHO criteria) using RNA-seq of the baseline tumour biopsy

  • Baseline transcriptomic profile of resistance to 4 months of palbociclib and endocrine therapy defined as stable or progressive disease by ultrasound based on WHO criteria

  4 Months

Secondary Outcomes (9)

• To identify biomarkers of resistance to a 4-month preoperative treatment of endocrine therapy and palbociclib by correlating tumour response by ultrasound (mandatory) or magnetic resonance (optional) imaging

  4 Months

• To identify biomarkers of resistance to a 4-month preoperative treatment of palbociclib plus endocrine therapy defined as residual disease burden, RCB of 3 using RNA-seq of the baseline tumour biopsy

  4 Months

• To identify biomarkers of resistance to a 4-month preoperative treatment of endocrine therapy and palbociclib defined as GGI high by RNA-seq of the residual tumour at surgery using RNA-seq of the baseline tumour biopsy

  4 Months

• To understand mechanisms of resistance to the combination of endocrine therapy and palbociclib by comparing the transcriptome of tumours at baseline and at surgery using RNA-seq

  4 Months

• To evaluate the safety of the combination of palbociclib plus endocrine therapy as assessed by the NCI-CTCAE version 4.03

  4 Months

Other Outcomes (6)

• To compare changes in clonal composition, transcriptomic changes and changes in the open chromatin state of tumour cells

  4 Months

• To compare changes in clonal composition, transcriptomic changes and changes in the open chromatin state of tumour cells

  4 Months

• Distant relapse-free survival (DRFS)

  36 months

Study Arms (1)

Palbociclib with Endocrine Therapy

EXPERIMENTAL

All subjects will receive palbociclib 125 mg for 4 cycles, orally, once a day, for 21 days followed by 7 days of rest (4 cycles of 28 day long). After the final rest week (therefore post cycle 4), subjects will receive 3 to 7 additional days of palbociclib, as necessary, at the same dose and posology, until the day before curative intent surgery. Depending upon the menopausal status, the patient will receive either letrozole or tamoxifen continuously during the palbociclib treatment (which consists of 4 cycles of 28 days).

Drug: Palbociclib

Interventions

Palbociclib DRUG

Each cycle will be 28 days. Patient will take study drug daily during 21 days and then have a rest period of 7 days.

Also known as: PD-0332991, Ibrance

Palbociclib with Endocrine Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female
• Age ≥ 18 years
• Histological diagnosis of breast adenocarcinoma that is estrogen receptor-positive, and HER2- negative as per the updated American Society of Clinical Oncology (ASCO) - College of American Pathologists (CAP) guidelines according to local testing.
• Multifocal unilateral or bilateral breast adenocarcinoma tumours are allowed provided that all tested foci are ER-positive and HER2-negative.
• ER-positive (ER+ is defined as having a IHC of 1% or more and/or and Allred of 2 or more and HER2-negative.
• HER2 negative (HER2 negative is defined as having an IHC of 1+ without ISH OR IHC 2+ and ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 4 signals/cells OR ISH non-amplified with ratio less than 2.0 and if reported, average HER2 copy number \< 4 signals/cells (without IHC)
• A primary non metastatic or locally advanced tumour of more than 2 cm (T2 or T3), N0 or N1 without prior treatment candidate for preoperative treatment
• ECOG Performance Status (PS) 0 or 1.
• Adequate Bone Marrow Function including:
• Absolute Neutrophil Count (ANC) ≥1500/μL or ≥1.5 x109/L;
• Platelets ≥100000/μL or ≥100 x 109/L;
• Hemoglobin ≥ 9 g/dL.
• Adequate Renal Function including: Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated creatinine clearance ≥ 60 ml/min as calculated using the method standard for the institution.
• Adequate Liver Function, including all of the following parameters:
• Total serum bilirubin ≤ 1.0 x ULN unless the subject has documented Gilbert syndrome (in which case up to 3 x ULN is acceptable) ;

You may not qualify if:

• Clinical T4 disease including inflammatory breast cancer.
• Prior history of invasive cancer including breast cancer except basal or squamous cell carcinoma of skin that has been definitively treated.
• Known hypersensitivity to the study drugs or excipients.
• Any illness or medical condition that is unstable or could jeopardize the safety of the subject or her compliance with study requirements.
• Subjects unable to swallow oral medications.
• Prior intake of letrozole, or any CDK inhibitor or anti-cancer therapy.
• Concurrent treatment with any of the drugs not permitted, i.e. strong CYP3A inhibitors/inducers and drugs known to cause QTc interval prolongation (see section 5.7 for specific instructions).
• QTc exceeding 480 msec, family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes (TdP).
• Uncontrolled diabetes, according to investigator's clinical judgment.
• Pregnant or lactating women.

Sponsors & Collaborators

• Jules Bordet Institute: lead

Study Sites (5)

Institut Jules Bordet

Anderlecht, 1070, Belgium

Location

CHU Brugmann

Brussels, 1090, Belgium

Location

CHU Saint-Luc

Brussels, 1200, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

CHU UCL Namur Sainte-Elisabeth

Namur, 5000, Belgium

Location

Related Publications (2)

• Papagiannis A, Majjaj S, Duhoux FP, Agostinetto E, Stanciu AM, Vanhulst T, Buisseret L, Larsimont D, Veys I, Paesmans M, Hammer TB, Awada A, Ameye L, Rothe F, Madriles F, Cash TP, Salgado R, Willard-Gallo K, Sotiriou C, Vuylsteke P, Neven P, Ignatiadis M. Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study. Nat Commun. 2025 Nov 26;16(1):11659. doi: 10.1038/s41467-025-66590-2.

  PMID: 41298425 DERIVED

• Brandao M, Coens C, Ignatiadis M. Patient-reported outcomes and genomic signatures: tools to tailor adjuvant endocrine treatment? Ann Oncol. 2019 Nov 1;30(11):1677-1681. doi: 10.1093/annonc/mdz404. No abstract available.

  PMID: 31613310 DERIVED

MeSH Terms

Interventions

palbociclib

Study Officials

• Michail Ignatiadis, MD

  Jules Bordet Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2017
• First Posted: February 28, 2017
• Study Start: July 5, 2017
• Primary Completion: March 28, 2019
• Study Completion: February 1, 2023
• Last Updated: April 19, 2023

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5)