Evaluating the Addition of Elacestrant (Oral SERD) to Niraparib (PARP-inhibitor) in Patients With Advanced/Metastatic HR+/HER2- Breast Cancer — ELEMENT  

BRCA1 Mutation Clinical Trial

Official title: Phase II Study Evaluating the Addition of Elacestrant, an Oral Selective Estrogen Receptor Degrader (SERD), to Niraparib, a PARP-inhibitor, Compared to Niraparib Alone in Patients With Hormone Receptor (HR)-Positive, HER2-negative Locally Advanced or Metastatic Breast Cancer With g/tBRCA1/2 and/or g/tPALB2 Mutations

Status Not yet recruiting

Clinical Trial Summary

Trial design:

Phase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with g/tBRCA1/2 or g/tPALB2 mutation, with 2:1 randomization into Arm A (niraparib + elacestrant) or arm B (niraparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.

Trial population:

Patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with g/tBRCA1/2 or g/tPALB2 mutation, having received at least one prior line of chemotherapy or endocrine-based therapy for irresectable, locally advanced, or metastatic disease (or adjuvant treatment with CDK4/6 inhibitor therapy), with ECOG performance status of 0-2 and life expectancy of > 6 months, with normal bone marrow and kidney functions and no active or newly diagnosed central nervous system (CNS) metastases or symptomatic metastatic visceral disease at risk of life-threatening complications.

Interventions:

Patients randomized to Arm A will receive 200mg niraparib daily and 400mg elacestrant daily, while patients randomized to Arm B will receive 200mg niraparib daily. Blood tests (hematology, biochemistry) will be performed at the beginning of every cycle, and imaging for tumor assessment (chest and abdominopelvic imaging) as well as QoL assessments will be performed every three months and in case of suspicion of progression/end of study.

Clinical Trial Description

Patients with HR-positive, HER2-negative advanced or metastatic breast cancer and g/tBRCA1/2 and/or g/tPALB2 mutations have a low progression-free survival (PFS) and represent a patient population with a high unmet need, hence further treatment options should be explored to improve patient outcomes.

Elacestrant is a novel, nonsteroidal, orally bioavailable estrogen receptor antagonist (SERD) that has shown efficacy in heavily pretreated patients with HR-positive, HER2-negative breast cancer, and in those with ESR1 mutations known to confer endocrine resistance, and has thus gained approval in 2023 by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of ET.

Niraparib is a poly-adenosine diphosphate ribose polymerase (PARP) inhibitor that has shown promise in patients with gBRCA mutated, HER2-negative locally advanced or metastatic breast cancer, previously treated with ≤2 prior lines of chemotherapy, as well as in patients with platinum-sensitive, recurrent ovarian cancer, regardless of the presence or absence of gBRCA1/2 mutations, with moderate bone marrow toxicity.

The purpose of the proposed study is to investigate if the addition of elacestrant to niraparib could potentially lead to an improvement in PFS compared to niraparib alone in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with g/tBRCA1/2 and/or g/tPALB2 mutations.

ELEMENT is a phase II, prospective, multi-center, randomized, open label, parallel group study in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with g/tBRCA1/2 or g/tPALB2 mutation, with 2:1 randomization into Arm A (niraparib + elacestrant) or arm B (niraparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study. ;

Related Conditions & MeSH terms

• Advanced or Metastatic Breast Cancer
• BRCA1 Mutation
• BRCA2 Mutation
• Breast Neoplasms
• Hormone Receptor Positive HER-2 Negative Breast Cancer
• PALB2 Gene Mutation

• NCT number: NCT06201234
• Study type: Interventional
• Source: German Breast Group
• Contact: Nader Hirmas, MD/PhD
• Phone: +49 61027480
• Email: element@gbg.de
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 31, 2024
• Completion date: March 31, 2028