Niraparib Plus Aromatase Inhibitors for Luminal-like(HER2-,ER+) and gBRCA or HDR+ Metastatic Breast Cancer (LUZERN)

NCT04240106 | Completed Phase 2

• 2 other identifiers: MedOPP1902017-004323-72
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 10

Brief Summary

This study evalues the efficacy -as determined by the clinical benefit rate (CBR)- of niraparib in combination with AIs in unresectable locally advanced or metastatic HR-positive/HER2-negative breast cancer patients harboring either gBRCAms or gBRCAwt and HRD. The planned number of patients is 23. Investigational product is Niraparib and will be administered daily continuously in 28-day cycles plus aromatase Inhibitors. Total study duration is 36 months and until 5 years of follow up.

Conditions

Breast Cancer; Breast Cancer Metastatic

Keywords

BRCA mutations; homologous recombination deficiency; Luminal like

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate (CBR) of niraparib in combination with AIs in unresectable locally advanced or metastatic HR-positive/HER2-negative breast cancer patients harboring either gBRCAms or gBRCAwt and HRD

  The CBR as best response, defined as the percentage of patients who experience a complete response, partial response or stable disease for at least 24 weeks and assessed by modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) criteria

  Baseline up to 24 weeks

Secondary Outcomes (6)

• Efficacy determinated by the Progression-free Survival (PFS)

  Baseline up to 36 months

• Efficacy determinated by the Objective Response Rate (ORR)

  Baseline up to 36 months

• Efficacy determined by Duration of Response (DoR)

  Baseline up to 36 months

• Efficacy determined by Overall survival (OS)

  Baseline up to 36 months

• Efficacy determined by Time to response (TTR)

  Baseline up to 36 months

Study Arms (1)

Niraparib in combination with Aromatase Inhibitors

EXPERIMENTAL

Upon meeting all selection criteria, patients enrolled in the study will receive the combination of niraparib orally, once daily, flat- fixed, continuously in 28-day cycles plus aromatase Inhibitors.

Drug: Niraparib; Drug: Aromatase Inhibitors

Interventions

Niraparib DRUG

Niraparib orally daily beginning on Day 1 and continuing through Day 28 of every 28-day cycle.

Also known as: ZEJULA

Niraparib in combination with Aromatase Inhibitors

Aromatase Inhibitors DRUG

Aromatase Inhibitors beginning on Day 1 and continuing through Day 28 of every 28-day cycle.

Niraparib in combination with Aromatase Inhibitors

Eligibility Criteria

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

You may qualify if:

• \. Patients have been informed about the nature of study, including the exploratory sub-study and has agreed to participate and signed the informed consent prior to participation in any study related activities.
• \. Male or female patients ≥ 18 years of age.
• \. Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 which the Investigator believes is stable at the time of screening.
• \. Life expectancy ≥16 weeks.
• \. Patients have a histologically and/or cytologically confirmed diagnosis of breast cancer.
• \. Patients have radiologic evidence of inoperable locally recurrent or metastatic breast cancer (MBC) that are not candidates for curative intent.
• \. Patients have human epidermal growth factor receptor 2 (HER2)- negative breast cancer (based on most recently analyzed biopsy) defined as a negative in situ hybridization (ISH) test or an immunohistochemistry (IHC) status of 0, 1+, or 2+ (if IHC 2+, a negative ISH test is required) by local laboratory testing.
• \. Patients have hormone receptor (HR)-positive breast cancer (based on most recently analyzed biopsy) defined as estrogen receptor (ER) and/or progesterone receptor (PgR) with ≥10% of tumor cells positive for ER and/or PgR by IHC irrespective of staining intensity.
• \. \[Cohort A\]: Patients with documented germinal mutation in BRCA1 or BRCA2 genes that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Patients with germinal mutations in BRCA1 or BRCA2 genes (gBRCAms) that are considered to be nondetrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism," etc.) will not be eligible for the study. Germinal BRCA1/2 results preceding the ICF signature will be accepted, as long as the results are documented and captured in the medical record during the pre-screening period.
• \. \[Exploratory cohort B\]: : Patients with either germinal BRCA1/2 wild-type (gBRCAwt) or gBRCAms that are considered to be nondetrimental (e.g., "Variants of uncertain clinical significance" or "Variant of unknown significance" or "Variant, favor polymorphism" or "benign polymorphism," etc.) and homologous recombination deficiency (HRD) based on the Myriad myChoice® CDx PLUS test. HRD status will be centrally confirmed both on the most recent tumor tissue since last progression (from either metastasis or primary tumor) and blood samples. Patients with a Myriad myChoice® CDx PLUS score of ≥ 25 or greater will be considered to have an abnormal HRR pathway and defined as HRD.
• \. \[Exploratory cohort B\]: Willingness and ability to provide additional six formalin-fixed paraffin-embedded (FFPE) tissue slides from the most recent tumor tissue since last progression (from either metastasis or primary tumor) to centrally perform the assay. It is strongly recommended obtaining six consecutive sections from the same tissue block used for the determination of HRD status.
• \. At least one and up to two prior lines of endocrine therapy (aromatase inhibitors \[AIs\] or fulvestrant) for treatment of locally recurrent and/or metastatic disease (except for patients progressing in the neoadjuvant or adjuvant setting).
• \. Confirmed disease progression while in the last AI-containing regimen (not necessarily in the treatment line immediately prior to study entry) with secondary endocrine resistance criteria.
• \. Patients may have progressed on no more than one chemotherapy regimens in the metastatic setting.
• \. The following will not be counted as a prior line of cytotoxic chemotherapy:

You may not qualify if:

• \. HER2-positive disease based on local laboratory results (performed by IHC/in situ hybridization test) or unknown HER2 status.
• \. Patients that are candidates for a local treatment with a radical intention.
• \. Patients that have previously received any PARP inhibitor (PARPi), including niraparib, in metastatic setting. Note: Patients treated with PARPi on (neo)adjuvant regimen with disease-free interval greater than 24 months following treatment interruption are eligible.
• \. Patients must not be simultaneously enrolled in any interventional clinical trial and must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is shorter, prior initiating protocol therapy.
• \. Patients who have had radiation therapy encompassing \>20% of the bone marrow within 2 weeks prior to start of treatment, excepting for palliative radiation therapy to a small field \>1 week prior to Day 1 of study.
• \. Patients with visceral crisis who require chemotherapy.
• \. Patients must not have a known hypersensitivity to niraparib components or excipients.
• \. Patients must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy.
• \. Patients must not have received colony-stimulating factors (e.g., Granulocyte colony-stimulating factor \[G-CSF\], granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 4 weeks prior initiating protocol therapy.
• \. Patients have had any known Grade 3 or 4 anemia, neutropenia or thrombocytopenia due to prior chemotherapy in adjuvant setting or cyclin-dependent kinases (CDK)4/6 inhibitors that persisted \> 4 weeks and was related to the most recent treatment.
• \. Patients must not have any known history of Myelodysplastic syndrome (MDS) or Acute myeloid leukemia (AML).
• \. Patients must not have a serious, uncontrolled medical disorder, nonmalignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (≤ 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan, any psychiatric disorder that prohibits obtaining informed consent, severe immunodeficiency disorders (i.e. human immunodeficiency virus \[HIV\] infection) or active hepatitis (i.e. Hepatitis B or C).
• \. Patients must not have had diagnosis, detection, or treatment of another type of cancer ≤ 2 years prior to initiating protocol therapy (except basal or squamous cell carcinoma of the skin, cervical carcinoma in situ and ductal carcinoma in situ \[DCIS\] definitively treated).
• \. PPatients with symptomatic uncontrolled brain metastases or leptomeningeal metastases. A scan to confirm the absence of brain metastases is not required. Patients with spinal cord compression unless considered to have received definitive treatment for this condition and have evidence of clinically stable disease (SD) for 35 days.
• \. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).

Sponsors & Collaborators

• MedSIR: lead
• GlaxoSmithKline: collaborator

Study Sites (10)

Centro Oncologico de Galicia

A Coruña, 15009, Spain

Location

Complejo Asistencial de Ávila

Ávila, 05071, Spain

Location

Hospital Uniersitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic i provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 28091, Spain

Location

Hospital Clinico San Carlos

Madrid, 28041, Spain

Location

Hospital Universitario 12 de octubre

Madrid, 28041, Spain

Location

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, 15706, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

niraparib; Aromatase Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• Antonio Llombart

  MedSIR

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Multicenter, open-label, single-arm, two-cohort, Simon's two- stage phase II clinical trial.

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 27, 2020
• Study Start: June 15, 2020
• Primary Completion: November 17, 2022
• Study Completion: November 17, 2023
• Last Updated: February 16, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10)