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

NCT06201234 | Recruiting Phase 2 DMC

• 1 other identifier: ELEMENT GBG-114
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 36

Brief 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). 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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)

  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

  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

  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

  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.

Study Arms (2)

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.

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.

Drug: Olaparib

Interventions

Olaparib + Elacestrant DRUG

Olaparib 600 mg orally daily and elacestrant 400 mg orally daily

Arm A: Olaparib + elacestrant*

Olaparib DRUG

Olaparib 600 mg orally daily

Arm B: Olaparib

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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)
• 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).

Sponsors & Collaborators

• GBG Forschungs GmbH: lead
• Stemline Therapeutics, Inc.: collaborator

Study Sites (36)

Vinzenz Von Paul Kliniken gGmbH - Marienhospital

Stuttgart, Baden-Wurttemberg, Germany

RECRUITING

University Hospital Tübingen

Tübingen, Baden-Wurttemberg, 72076, Germany

RECRUITING

Rems-Murr-Klinik-Winnenden

Winnenden, Baden-Wurttemberg, Germany

RECRUITING

GRN Klinik Weinheim

Weinheim, Baden-Württembergs, 69469, Germany

RECRUITING

Hämatologie-Onkologie im Zentrum MVZ GmbH

Augsburg, Bavaria, 86150, Germany

RECRUITING

Klinikum Bayreuth

Bayreuth, Bavaria, Germany

RECRUITING

Schwerpunktpraxis der Gynäkologie und Onkologie

Fürstenwalde, Brandenburg, 15517, Germany

RECRUITING

Agaplesion Frankfurter Diakonie Kliniken gGmbH

Frankfurt am Main, Hesse, 60431, Germany

RECRUITING

Klinikum der J. W. Goethe Universität

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

Klinikum Kassel GmbH - Frauenklinik

Kassel, Hesse, 34125, Germany

RECRUITING

St. Josefs-Hospital, Gynäkologie und Geburtshilfe

Wiesbaden, Hesse, 65189, Germany

RECRUITING

Studien GbR Braunschweig

Braunschweig, Lower Saxony, 38100, Germany

RECRUITING

MVZ Onkologische Kooperation Harz GbR

Goslar, Lower Saxony, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

RECRUITING

Universitätsklinik Köln

Cologne, North Rhine-Westphalia, Germany

NOT YET RECRUITING

Heinrich-Heine-Universität Düsseldorf

Düsseldorf, North Rhine-Westphalia, 40225, Germany

RECRUITING

Zentrum für Gynäkologische Onkologie am MVZ Medical Center Düsseldorf GmbH

Düsseldorf, North Rhine-Westphalia, 40235, Germany

RECRUITING

KEM Kliniken Essen-Mitte GmbH

Essen, North Rhine-Westphalia, 45136, Germany

RECRUITING

Marienhospital Witten

Witten, North Rhine-Westphalia, 58452, Germany

RECRUITING

Helios Universitätsklinikum Wuppertal

Wuppertal, North Rhine-Westphalia, 42283, Germany

RECRUITING

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR

Mainz, Rhineland-Palatinate, 55131, Germany

RECRUITING

Institut für Versorgungsforschung Mayen

Mayen, Rhineland-Palatinate, Germany

RECRUITING

Caritas Traegergesellschaft Saarbruecken mbH (CTS)

Saarbrücken, Saarland, 66113, Germany

RECRUITING

University Hospital Carl Gustav Carus

Dresden, Saxony, 01307, Germany

RECRUITING

Gemeinschaftspraxis Dr.Illmer, Dr. Wolf, Dr. Jacobasch, Dr. Freiberg-Richter

Dresden, Saxony, Germany

RECRUITING

Universität Leipzig

Leipzig, Saxony, Germany

RECRUITING

MediOnko-Institut GbR

Berlin, State of Berlin, 10367, Germany

RECRUITING

Das Brust Zentrum - Die Frauenärzte

Berlin, State of Berlin, 12623, Germany

RECRUITING

Marienhospital Bottrop gGmbH

Bottrop, 46236, Germany

RECRUITING

Universitätsklinikum Essen - Klinik für Frauenheilkunde und Geburtshilfe

Essen, 45147, Germany

RECRUITING

National Center for Tumor Diseases Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitätsklinikum des Saarlandes - Frauenklinik

Homburg, 66424, Germany

RECRUITING

Rotkreuzklinikum München

München, 80634, Germany

RECRUITING

Studienzentrum Onkologie Ravensburg

Ravensburg, 88212, Germany

RECRUITING

Robert Bosch Gesellschaft fuer medizinische Forschung mbH

Stuttgart, Germany

RECRUITING

Klinikum Worms

Worms, 67550, Germany

RECRUITING

Related Publications (4)

• 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. Erratum In: J Clin Oncol. 2023 Aug 10;41(23):3962. doi: 10.1200/JCO.23.01239.

  PMID: 35584336 BACKGROUND

• Robson 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.

  PMID: 28578601 BACKGROUND

• Gelmon 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.

  PMID: 34087573 BACKGROUND

• Bardia 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.

  PMID: 33513026 BACKGROUND

Related Links

• Website of German Breast Group

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

olaparib; elacestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sibylle Loibl, MD, PhD

  Prof., MD ASCO, ESGO, ESMO, DKG, DGGG, AGO, DGS, BIG, BCIRG, St. Gallen Faculty Member, SABCS Faculty member

  STUDY CHAIR

Central Study Contacts

Laura Steinmann

CONTACT

+49 61027480; element@gbg.de

Stefan Schoeffel

CONTACT

+49 61027480; element@gbg.de

Study Design

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

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: January 11, 2024
• Study Start: December 13, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: December 1, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning after final analysis and publication of all secondary efficacy endpoints; no end date.
• Access Criteria: Who: Researchers who provide translational research proposals. Proposals should be approved by the GBG scientific board. What: Individual participant data that underlie the results reported in this article, after final analysis and publication of all secondary efficacy endpoints. How: Proposal forms should be requested from trafo@gbg.de; once the application has been approved and a data transfer agreement has been signed, researchers will be given access to the data.

Locations

DE (36)