Hormone Receptor Positive HER-2 Negative Breast CancerPhase 2ELEMENTNCT06201234
Evaluating the Addition of Elacestrant (Oral SERD) to Olaparib (PARP-inhibitor) in Patients With Advanced/Metastatic HR+/HER2- Breast Cancer
A Phase 2 study testing Olaparib + Elacestrant and Olaparib in people with Hormone Receptor Positive HER-2 Negative Breast Cancer and Advanced or Metastatic Breast Cancer, run by GBG Forschungs GmbH at 36 sites in Germany.
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 gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hormone Receptor Positive HER-2 Negative Breast Cancer, Advanced or Metastatic Breast Cancer, BRCA1 Mutation
- What is being tested?
- Olaparib + Elacestrant and Olaparib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 176 participants
- Where
- 36 sitesGermany
- Study dates
- 13 Dec 2024to 31 Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for study participation only if they comply with the following criteria:
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for scheduled visit, the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Female or male patients.
- Age at study entry of at least 18 years.
- Locally advanced or metastatic breast cancer that is HR-positive (ER and/or PgR ≥ 10% of stained cells at IHC) and HER2-negative (IHC 0 or 1+, or 2+ and ISH negative according to ASCO/CAP guidelines).
- Patients with deleterious or suspected deleterious gBRCA1/2 mutation detected upon local testing.
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- Willingness and ability to provide archived formalin fixed paraffin embedded tissue (FFPE) block or a partial block from archived tumor or metastasis.
- Indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.
- Resolution of all acute toxic effects of prior anti-cancer therapy including endocrine therapy or surgical procedures to NCI CTCAE version 5.0 grade ≤ 1 (except alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion).
- Life-expectancy > 6 months.
- For female patients: patients of childbearing potential (defined as not post-menopausal and not permanently sterile [latter defined as having undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy]) require a negative serum or urinary pregnancy test within 72 hours before starting treatment in this study (in this case, patients need to use highly effective non-hormonal contraceptive methods as specified in the protocol).
- For male patients: during the intervention period and for at least 120 days after the last dose of elacestrant, patients should refrain from heterosexual intercourse or use a condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak), and they should refrain from donating sperm.
Who cannot join
- Patients will be ineligible for study participation if they fulfill any of the following criteria:
- Known hypersensitivity reaction to one of the compounds, excipients, or substances used in this protocol.
- Active or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, carcinomatous meningitis, or radiographic signs of CNS hemorrhage. Note: Patients with stable brain metastases are allowed. Radiotherapeutic treatment must be completed 1 week before planned day 1 of study therapy.
- Presence of symptomatic metastatic visceral disease that are at risk of life-threatening complications in the short term, including but not confined to massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or fulminant liver involvement.
- Inadequate organ function prior to enrolment including:
- Hemoglobin < 9 g/dL (< 5.6 mmol/L)
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- Absolute neutrophil count (ANC) < 1500/mm³ (< 1.5 x 109/L)
- Platelets < 100,000/mm³ (< 100 x 109/L)
- Alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) > 3 x upper normal limits (ULN). If the patient has liver metastases, ALT and AST should not be ≥ 5 x ULN.
- Alkaline phosphatase (ALP) > 2.5 x ULN
- Total serum bilirubin > 1.5 x ULN (exception: patients with Gilbert's syndrome permitted up to ≤ 3 x ULN)
- Serum creatinine > 1.5 x ULN or estimated creatinine clearance < 50 mL/min as calculated using the standard method for the institution.
- Existing contraindication against the use of the elacestrant or olaparib.
- Prior treatment with PARP inhibitors.
- Female patients: pregnancy or lactation at the time of randomization or intention to become pregnant during the study and for a predefined period after the end of treatment (as described in protocol).
- Male patients: intention to get a child during the study and for a predefined period after the end of treatment (as described in protocol).
- According to the treatment received during the study, required contraception timelines for female and male patients are described in the study protocol.
- Any of the following within 6 months prior to enrolment: myocardial infarction, severe/unstable angina, ongoing grade ≥ 2 cardiac dysrhythmias, prolonged QT corrected by Fridericia's formula (QTcF) grade ≥ 2, uncontrolled atrial fibrillation of any grade, coronary/peripheral artery bypass graft, heart failure of New York Heart Association (NYHA) Class II or greater, or cerebrovascular accident including transient ischemic attack.
- Uncontrolled hypertension at the time of screening (systolic BP > 140 mmHg or diastolic BP > 90 mmHg that has not been adequately treated or controlled).
- Active and current anticoagulation for treatment purposes of thrombotic events occurring < 6 months before enrolment is not allowed (prophylactic anticoagulation, however, is acceptable). Treatment with an anticoagulant for a thrombotic event occurring > 6 months before enrolment, or for an otherwise stable and allowed medical condition (e.g., well controlled atrial fibrillation) is acceptable, provided dose and coagulation parameters (as defined by local standard of care) are stable for at least 28 days prior to the first dose of study drug.
- Known difficulty in tolerating oral medications or conditions which would impair absorption of oral medications such as: uncontrolled nausea or vomiting (i.e., CTCAE ≥ grade 3 despite antiemetic therapy), ongoing gastrointestinal obstruction/motility disorder, malabsorption syndrome, or prior gastric bypass.
- History of endometrial intraepithelial neoplasia in patients who have not undergone a hysterectomy.
- Malignant disease other than breast cancer, active or being disease-free for less than 5 years (except carcinoma in situ of the cervix, DCIS, and non-melanomatous skin cancer adequately treated).
- Uncontrolled significant active infections including HBV, HCV, and/or HIV. Patients with a positive hepatitis B surface antigen result or a positive hepatitis C antibody test result at screening or within 3 months before first dose of study treatment are excluded, except for the following:
- Participants with positive anti-HBs antibody titer and confirmatory negative hepatitis B DNA polymerase chain reaction.
- Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if they have both completed curative therapy and have a hepatitis C viral load < quantifiable limit.
- Any severe, acute, uncontrolled, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational or non-investigational products administration, or may interfere with the interpretation of study results, and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Moreover, patients who, by virtue of an order issued by judicial or administrative authorities, are committed to an institution or those who cannot take part in clinical trials are excluded from this study.
- History of significant neurological or psychiatric disorders including psychotic disorders, dementia, or seizures that would prohibit the understanding and giving of informed consent.
- Unable or unwilling to avoid medications, supplements (e.g., St. John's wort), or foods (e.g., grapefruit, pomegranate, pomelos, star fruit, Seville oranges and their juices) that are moderate/strong inhibitors or inducers of CYP3A4 activity. Participation will be allowed if the medication, supplements, or foods are discontinued for at least 14 days prior to study entry and for the duration of the study.
- Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
- Receipt of live attenuated vaccination within 30 days prior to study entry. COVID-19 vaccines that do not contain live viruses are allowed (at least one week prior to study entry).
Trial locations and contacts
36 sites in 1 country. Contact the study team or a site near you to ask about taking part.
36 sites in 1 country
Germany36 sites, 36 recruiting
- Recruiting
Hämatologie-Onkologie im Zentrum MVZ GmbH
Augsburg, Bavaria, 86150
Bernhard Heinrich, MD, bernhard.heinrich@hop-augsburg.de
- Recruiting
Klinikum Bayreuth
Bayreuth, Bavaria
Chritsoph Mundhenke, Prof. Dr., christoph.mundhenke@klinikum-bayreuth.de
- Recruiting
MediOnko-Institut GbR
Berlin, State of Berlin, 10367
Gülten Oskay-Öczelik, PD Dr., studienoskay@medionko.de
- Recruiting
Das Brust Zentrum - Die Frauenärzte
Berlin, State of Berlin, 12623
Dr. med. Antje Müller, 00491735447450, studienmueller@dasbrustzentrum.de
- Recruiting
Marienhospital Bottrop gGmbH
Bottrop, 46236
Hans-Christian Kolberg, MD, hans-christian.kolberg@mhb-bottrop.de
- Recruiting
Studien GbR Braunschweig
Braunschweig, Lower Saxony, 38100
Janine Kreiss-Sender, Dr., Kreiss-Sender@frauenaerzte-casparistr.de
- Not yet recruiting
Universitätsklinik Köln
Cologne, North Rhine-Westphalia
Kerstin Rhiem, Prof. Dr., kerstin.rhiem@uk-koeln.de
- Recruiting
University Hospital Carl Gustav Carus
Dresden, Saxony, 01307
Theresa Link, Dr., theresa.link@uniklinikum-dresden.de
- Recruiting
Gemeinschaftspraxis Dr.Illmer, Dr. Wolf, Dr. Jacobasch, Dr. Freiberg-Richter
Dresden, Saxony
Thomas Illmer, Dr., illmer@onkologie-dresden.net
- Recruiting
Heinrich-Heine-Universität Düsseldorf
Düsseldorf, North Rhine-Westphalia, 40225
Tanja Fehm, Prof, 00492118118483, tanja.fehm@med.uni-duesseldorf.de
- Recruiting
Zentrum für Gynäkologische Onkologie am MVZ Medical Center Düsseldorf GmbH
Düsseldorf, North Rhine-Westphalia, 40235
Dr. med. Athina Kostara, 004921144773368, athina.kostara@gynonco.de
- Recruiting
KEM Kliniken Essen-Mitte GmbH
Essen, North Rhine-Westphalia, 45136
Johanna Frindte, J.Frindte@kem-med.com
- Recruiting
Universitätsklinikum Essen - Klinik für Frauenheilkunde und Geburtshilfe
Essen, 45147
Ann-Kathrin Bittner, Prof. Dr., 00492017230, Ann-Kathrin.Bittner@uk-essen.de
- Recruiting
Agaplesion Frankfurter Diakonie Kliniken gGmbH
Frankfurt am Main, Hesse, 60431
Marc Thill, Prof. Dr., 00496995332228, marc.thill@agaplesion.de
Marc Thill, Prof. Dr.
- Recruiting
Klinikum der J. W. Goethe Universität
Frankfurt am Main, Hesse, 60590
Christine Solbach, Prof., Solbach@med.uni-frankfurt.de
- Recruiting
Schwerpunktpraxis der Gynäkologie und Onkologie
Fürstenwalde, Brandenburg, 15517
Georg Heinrich, Dr., g.heinrich@bngo.de
- Recruiting
MVZ Onkologische Kooperation Harz GbR
Goslar, Lower Saxony
Mark-Oliver Zahn, Dr., m-o.zahn@onkologie-goslar.de
- Recruiting
Medizinische Hochschule Hannover
Hanover, Lower Saxony
Won Park-Simon, Prof. Dr., Park-Simon.Tjoung-Won@mh-hannover.de
- Recruiting
National Center for Tumor Diseases Heidelberg
Heidelberg, 69120
Laura Michel, PD Dr., Laura.michel@med.uni-heidelberg.de
- Recruiting
Universitätsklinikum des Saarlandes - Frauenklinik
Homburg, 66424
Julia Radosa, Prof.Dr., 004968411628000, julia.radosa@uks.eu
- Recruiting
Klinikum Kassel GmbH - Frauenklinik
Kassel, Hesse, 34125
Lydia Dautzenberg, Dr. med., 00495619800, lydia.dautzenberg@gnh.net
- Recruiting
Universität Leipzig
Leipzig, Saxony
Dirk Forstmeyer, Dr., Forstmeyer.Studienmails@medizin.uni-leipzig.de
- Recruiting
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
Mainz, Rhineland-Palatinate, 55131
Marcus Schmidt, Prof. Dr., marcus.schmidt@unimedizin-mainz.de
- Recruiting
Institut für Versorgungsforschung Mayen
Mayen, Rhineland-Palatinate
Michael Maasberg, Dr., mail@dr-maasberg.de
- Recruiting
Rotkreuzklinikum München
München, 80634
Claus A Hanusch, Dr., claus.hanusch@swmbrk.de
- Recruiting
Studienzentrum Onkologie Ravensburg
Ravensburg, 88212
Thomas Decker, Prof. Dr., 004907513661970, Thomas.Decker@onkonet.eu
Thomas Decker, Prof. Dr.
- Recruiting
Caritas Traegergesellschaft Saarbruecken mbH (CTS)
Saarbrücken, Saarland, 66113
Mustafa Deryal, Dr., 00496814061301, m.deryal@caritasklinikum.de
- Recruiting
Vinzenz Von Paul Kliniken gGmbH - Marienhospital
Stuttgart, Baden-Wurttemberg
Manfred Hofmann, PD Dr., manfred.hofmann@vinzenz.de
- Recruiting
Robert Bosch Gesellschaft fuer medizinische Forschung mbH
Stuttgart
Lena Pfaff, Dr., Lena.Pfaff@rbk.de
- Recruiting
University Hospital Tübingen
Tübingen, Baden-Wurttemberg, 72076
Andreas Hartkopf, Prof. Dr., theresa.link@uniklinikum-dresden.de
- Recruiting
GRN Klinik Weinheim
Weinheim, Baden-Württembergs, 69469
Dr. med. Lelia-Eveline Bauer, 00496201892701, lelia.bauer@grn.de
- Recruiting
St. Josefs-Hospital, Gynäkologie und Geburtshilfe
Wiesbaden, Hesse, 65189
Antje Lehnert, Dr., alehnert@joho.de
- Recruiting
Rems-Murr-Klinik-Winnenden
Winnenden, Baden-Wurttemberg
Hans-Joachim Strittmatter, Prof Dr., Hans-Joachim.Strittmatter@rems-murr-kliniken.de
- Recruiting
Marienhospital Witten
Witten, North Rhine-Westphalia, 58452
Monika Graeser, PD Dr., Monika.Graeser@elisabethgruppe.de
- Recruiting
Klinikum Worms
Worms, 67550
Dr. med. Sebastian Züfle, sebastian.zuefle@klinikum-worms.de
- Recruiting
Helios Universitätsklinikum Wuppertal
Wuppertal, North Rhine-Westphalia, 42283
Vesna Bjelic-Radisic, Prof, Vesna.Bjelic-Radisic@helios-gesundheit.de
About this study
Official title: Phase II Study Evaluating the Addition of Elacestrant, an Oral Selective Estrogen Receptor Degrader (SERD), to Standard-of-care Olaparib in Patients With Hormone Receptor (HR)-Positive, HER2-negative Locally Advanced or Metastatic Breast Cancer With gBRCA1/2 Mutations
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 gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.
Read more
Trial population:
Patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutation, with an indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib, an 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 600 mg olaparib daily and 400 mg elacestrant daily, while patients randomized to Arm B will receive 600 mg olaparib 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.
Read the detailed description
Patients with HR-positive, HER2-negative advanced or metastatic breast cancer and gBRCA1/2 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.
Olaparib is approved by the EMA for deleterious or suspected deleterious gBRCA-mutated, HER2-negative metastatic BC, based on positive outcomes in the phase III OlympiAD trial which showed improved median PFS, response rates, and less toxicity with olaparib compared to SOC.
The purpose of the proposed study is to investigate if the addition of elacestrant to standard olaparib therapy could potentially lead to an improvement in PFS compared to olaparib alone in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 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 gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.
- Conditions
- Hormone Receptor Positive HER-2 Negative Breast Cancer, Advanced or Metastatic Breast Cancer, BRCA1 Mutation, BRCA2 Mutation
- Being tested
- Olaparib + Elacestrant, Olaparib
- Keywords
- Elacestrant, Olaparib, Breast cancer, Metastases, Palliative therapy
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olaparib + ElacestrantDrug
Olaparib 600 mg orally daily and elacestrant 400 mg orally daily
OlaparibDrug
Olaparib 600 mg orally daily
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Olaparib + elacestrant* | Experimental | Treatment will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.
* Together with GnRH analogue in pre- and perimenopausal women, and in men, at least two weeks prior to treatment.
* Elacestrant tablets 400 mg orally daily
* Olaparib 600 mg orally daily The protocol provides procedures for specific adverse events requiring dose modifications or delays. Receives: Drug: Olaparib + Elacestrant |
| Arm B: Olaparib | Active comparator | Treatment will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.
• Olaparib 600 mg orally once daily
The protocol provides procedures for specific adverse events requiring dose modifications or delays. Receives: Drug: Olaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS)
PFS, investigator-assessed. To evaluate the impact on PFS of elacestrant with olaparib compared to olaparib alone in patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutations.
Measured: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.
Secondary outcomes (10)
Time-to-treatment failure (TTF)
To compare TTF between treatment arms (i.e., elacestrant + olaparib vs. olaparib).
Measured: TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.
Overall survival (OS)
To compare OS between treatment arms.
Measured: OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
Patient reported outcome (PRO) in the form of quality of life (QoL) assessment
To assess and compare patient reported breast cancer-specific QoL as measured by FACT-ES questionnaire.
Measured: At baseline, day 1 of cycle 2 (each cycle is 28 days), every 3 months starting from treatment start, and at end of treatment (an average of 12 months per patient).
PFS in stratified and exploratory subgroups
To compare PFS in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no.
To compare PFS in the exploratory subgroups specified in the protocol.
Measured: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.
TTF in the stratified subgroups
To compare TTF in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no.
To compare TTF in the exploratory subgroups specified in the protocol.
Measured: TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.
OS in the stratified subgroups
To compare OS in the stratified subgroups: pre-treatment chemotherapy in the metastatic setting yes vs. no.
To compare OS in the exploratory subgroups specified in the protocol.
Measured: OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
Overall response rate (ORR)
To compare ORR between treatment arms.
Measured: ORR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, assessed up to 48 months.
Clinical benefit rate (CBR)
To compare the CBR between treatment arms.
Measured: CBR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, or stable disease for at least 24 weeks from randomization.
Numbers and types of adverse events as assessed by CTCAE v5.0
To assess and compare safety between treatment arms (frequency and severity of AEs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0).
Measured: During treatment phase, an average of 12 months per patient.
Compliance between treatment arms as assessed by treatment delays, reductions, and interruptions
Frequencies of patients whose treatment had to be reduced, delayed, interrupted, or prematurely discontinued will be reported for both arms, together with reasons for such modifications, and comparisons between the two arms will be conducted with the χ2-test with continuity correction.
Measured: During treatment phase, an average of 12 months per patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2024
- Study start13 Dec 2024
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hormone Receptor Positive HER-2 Negative Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 176 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GBG Forschungs GmbH
- Sponsor type
- University, hospital or other
- Collaborators
- Stemline Therapeutics, Inc.
- Responsible party
- Sponsor
- Investigators
- Sibylle Loibl, MD, PhD, Study chair, Prof., MD ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06201234
- Sponsor's protocol ID
- ELEMENT GBG-114
- Acronym
- ELEMENT
- Status last verified
- Nov 2025
- First submitted
- 7 Dec 2023
- Last updated
- 1 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article can be made available after final analysis and publication of all secondary efficacy endpoints.
Publications
Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, Garcia Saenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortes J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 Oct 1;40(28):3246-3256. doi: 10.1200/JCO.22.00338. Epub 2022 May 18.
PubMed 35584336Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.
PubMed 28578601Gelmon KA, Fasching PA, Couch FJ, Balmana J, Delaloge S, Labidi-Galy I, Bennett J, McCutcheon S, Walker G, O'Shaughnessy J; Collaborating Investigators. Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis. Eur J Cancer. 2021 Jul;152:68-77. doi: 10.1016/j.ejca.2021.03.029. Epub 2021 Jun 1.
PubMed 34087573Bardia A, Kaklamani V, Wilks S, Weise A, Richards D, Harb W, Osborne C, Wesolowski R, Karuturi M, Conkling P, Bagley RG, Wang Y, Conlan MG, Kabos P. Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer. J Clin Oncol. 2021 Apr 20;39(12):1360-1370. doi: 10.1200/JCO.20.02272. Epub 2021 Jan 29.
PubMed 33513026
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Evaluating the Addition of Elacestrant, an Oral Selective Estrogen Receptor Degrader (SERD), to Standard-of-care Olaparib in Patients With Hormone Receptor (HR)-Positive, HER2-negative Locally Advanced or Metastatic Breast Cancer With gBRCA1/2 Mutations
- ClinicalTrials.gov ID
- NCT06201234
- Acronym / sponsor ID
- ELEMENT / ELEMENT GBG-114
- Conditions
- Hormone Receptor Positive HER-2 Negative Breast Cancer, Advanced or Metastatic Breast Cancer, BRCA1 Mutation, BRCA2 Mutation
- Keywords
- Elacestrant, Olaparib, Breast cancer, Metastases, Palliative therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 176 participants (estimated)
- Lead sponsor
- GBG Forschungs GmbHUniversity, hospital or other
- Collaborators
- Stemline Therapeutics, Inc.
- Study start
- 13 Dec 2024 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 11 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). 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 gBRCA1/2 mutation, with an indication for standard-of-care PARP inhibitor therapy and planned treatment with olaparib, an 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 600 mg olaparib daily and 400 mg elacestrant daily, while patients randomized to Arm B will receive 600 mg olaparib 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.
Detailed description
Patients with HR-positive, HER2-negative advanced or metastatic breast cancer and gBRCA1/2 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.
Olaparib is approved by the EMA for deleterious or suspected deleterious gBRCA-mutated, HER2-negative metastatic BC, based on positive outcomes in the phase III OlympiAD trial which showed improved median PFS, response rates, and less toxicity with olaparib compared to SOC.
The purpose of the proposed study is to investigate if the addition of elacestrant to standard olaparib therapy could potentially lead to an improvement in PFS compared to olaparib alone in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 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 gBRCA1/2 mutation, with 2:1 randomization into Arm A (olaparib + elacestrant) or arm B (olaparib). Treatment in either arm will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Olaparib + elacestrant* | Experimental | Drug: Olaparib + ElacestrantTreatment will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study. * Together with GnRH analogue in pre- and perimenopausal women, and in men, at least two weeks prior to treatment. * Elacestrant tablets 400 mg orally daily * Olaparib 600 mg orally daily The protocol provides procedures for specific adverse events requiring dose modifications or delays. |
| Arm B: Olaparib | Active comparator | Drug: OlaparibTreatment will be given until disease progression, unacceptable toxicity, withdrawal of patient´s consent to study participation, or end of study. • Olaparib 600 mg orally once daily The protocol provides procedures for specific adverse events requiring dose modifications or delays. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients will be eligible for study participation only if they comply with the following criteria:
- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for scheduled visit, the treatment and follow-up, must be obtained and documented according to the local regulatory requirements.
- Female or male patients.
- Age at study entry of at least 18 years.
- Locally advanced or metastatic breast cancer that is HR-positive (ER and/or PgR ≥ 10% of stained cells at IHC) and HER2-negative (IHC 0 or 1+, or 2+ and ISH negative according to ASCO/CAP guidelines).
Key exclusion criteria (31 listed)
- Patients will be ineligible for study participation if they fulfill any of the following criteria:
- Known hypersensitivity reaction to one of the compounds, excipients, or substances used in this protocol.
- Active or newly diagnosed CNS metastases, including leptomeningeal carcinomatosis, carcinomatous meningitis, or radiographic signs of CNS hemorrhage. Note: Patients with stable brain metastases are allowed. Radiotherapeutic treatment must be completed 1 week before planned day 1 of study therapy.
- Presence of symptomatic metastatic visceral disease that are at risk of life-threatening complications in the short term, including but not confined to massive uncontrolled effusions (peritoneal, pleural, pericardial), pulmonary lymphangitis, or fulminant liver involvement.
- Inadequate organ function prior to enrolment including:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olaparib + ElacestrantOlaparib 600 mg orally daily and elacestrant 400 mg orally daily | Drug | Arm A: Olaparib + elacestrant* |
| OlaparibOlaparib 600 mg orally daily | Drug | Arm B: Olaparib |
Primary outcome
Progression free survival (PFS)
Time frame: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.
PFS, investigator-assessed. To evaluate the impact on PFS of elacestrant with olaparib compared to olaparib alone in patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer with gBRCA1/2 mutations.
10 secondary outcomes
Time-to-treatment failure (TTF)
Time frame: TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.
Overall survival (OS)
Time frame: OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
Patient reported outcome (PRO) in the form of quality of life (QoL) assessment
Time frame: At baseline, day 1 of cycle 2 (each cycle is 28 days), every 3 months starting from treatment start, and at end of treatment (an average of 12 months per patient).
PFS in stratified and exploratory subgroups
Time frame: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.
TTF in the stratified subgroups
Time frame: TTF is defined as time from randomization to discontinuation of treatment due to disease progression, treatment toxicity, patient´s preference, or death, assessed up to 48 months.
OS in the stratified subgroups
Time frame: OS is defined as the time from randomization to death due to any reason, assessed up to 48 months.
Overall response rate (ORR)
Time frame: ORR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, assessed up to 48 months.
Clinical benefit rate (CBR)
Time frame: CBR is defined as the percentage of patients who have achieved either a confirmed complete response or partial response, or stable disease for at least 24 weeks from randomization.
Numbers and types of adverse events as assessed by CTCAE v5.0
Time frame: During treatment phase, an average of 12 months per patient.
Compliance between treatment arms as assessed by treatment delays, reductions, and interruptions
Time frame: During treatment phase, an average of 12 months per patient.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2025.
- Background: PubMed 35584336Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, Mouret-Reynier MA, Sohn JH, Taylor D, Harnden KK, Khong H, Kocsis J, Dalenc F, Dillon PM, Babu S, Waters S, Deleu I, Garcia Saenz JA, Bria E, Cazzaniga M, Lu J, Aftimos P, Cortes J, Liu S, Tonini G, Laurent D, Habboubi N, Conlan MG, Bardia A. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022 Oct 1;40(28):3246-3256. doi: 10.1200/JCO.22.00338. Epub 2022 May 18.
- Background: PubMed 28578601Robson M, Im SA, Senkus E, Xu B, Domchek SM, Masuda N, Delaloge S, Li W, Tung N, Armstrong A, Wu W, Goessl C, Runswick S, Conte P. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017 Aug 10;377(6):523-533. doi: 10.1056/NEJMoa1706450. Epub 2017 Jun 4.
- Background: PubMed 34087573Gelmon KA, Fasching PA, Couch FJ, Balmana J, Delaloge S, Labidi-Galy I, Bennett J, McCutcheon S, Walker G, O'Shaughnessy J; Collaborating Investigators. Clinical effectiveness of olaparib monotherapy in germline BRCA-mutated, HER2-negative metastatic breast cancer in a real-world setting: phase IIIb LUCY interim analysis. Eur J Cancer. 2021 Jul;152:68-77. doi: 10.1016/j.ejca.2021.03.029. Epub 2021 Jun 1.
- Background: PubMed 33513026Bardia A, Kaklamani V, Wilks S, Weise A, Richards D, Harb W, Osborne C, Wesolowski R, Karuturi M, Conkling P, Bagley RG, Wang Y, Conlan MG, Kabos P. Phase I Study of Elacestrant (RAD1901), a Novel Selective Estrogen Receptor Degrader, in ER-Positive, HER2-Negative Advanced Breast Cancer. J Clin Oncol. 2021 Apr 20;39(12):1360-1370. doi: 10.1200/JCO.20.02272. Epub 2021 Jan 29.
- Website of German Breast GroupLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article can be made available after final analysis and publication of all secondary efficacy endpoints.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Sibylle Loibl, MD, PhD study chair
Prof., MD ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member
36 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Olaparib + Elacestrant and Olaparib in people with Hormone Receptor Positive HER-2 Negative Breast Cancer and Advanced or Metastatic Breast Cancer, run by GBG Forschungs GmbH at 36 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 36 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laura Steinmann (+49 61027480 ext. 0, element@gbg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) (time frame: PFS is defined as the time from randomization to first progression as assessed by the investigator, or death, whichever occurs first, assessed up to 48 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06201234, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2025.