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NeoplasmsPhase 1NCT02123823

BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

A Phase 1 study testing Everolimus, Exemestane and BI 836845 in people with Neoplasms, run by Boehringer Ingelheim at 38 sites in 10 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Phase Ib / II study to determine the Maximum Tolerated Dose and Recommended Phase II Dose, and to evaluate the safety and antitumour activity, of BI 836845 and everolimus in combination with exemestane in women with HR+/HER2- advanced breast cancer Read more about this study

Who is it for?
Ages 18 to 99 years, women only
Conditions the study is for
Neoplasms
What is being tested?
Everolimus, Exemestane and BI 836845
Could I receive a placebo?
No, everyone receives an active treatment
How many people
164 participants
Where
38 sitesin 10 countries
Study dates
15 May 2014to 14 Dec 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 99 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically-confirmed locally advanced (aBC) or metastatic breast cancer (mBC) not deemed amenable to curative surgery or curative radiation therapy
  • Tumors are positive for estrogen-receptor (ER) and/or progesterone receptor (PgR).
  • Tumors must be negative for HER2 per local lab testing.
  • Must have adequate archival tumor tissue from surgery or biopsy.
  • Postmenopausal female patients aged >=18 years old.
  • Objective evidence of recurrence or progressive disease on or after the last line of systemic therapy for breast cancer prior to study entry
Show all 17Show fewer
  • The patient is disease refractory to non-steroidal aromatase inhibitor (letrozole and/or anastrozole)
  • Patients must have: a) Measurable lesion according to RECIST version 1.1 (R09-0262) or b) Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable lesion as defined above
  • Eastern Cooperative Oncology Group performance score <= 2.
  • Life expectancy of >= 6 months in the opinion of the investigator
  • Fasting plasma glucose < 8.9 mmol/L (< 160 mg/dL) and HbA1c < 8.0%
  • Adequate organ function
  • Recovered from any previous therapy related toxicity to <= Grade 1 at study entry (except for stable sensory neuropathy <=Grade 2 and alopecia)
  • Written informed consent that is consistent with ICH-GCP guidelines and local regulations
  • Inclusion criteria for the biopsy substudy are identical to the main study of the phase II part except for the following two inclusion criteria:
  • Fresh tumor biopsy should be taken when deemed safe and feasible by the investigator and upon informed consent by the patient. Bone lesion is not recommended for biopsy
  • Patients eligible to undergo tumor biopsy should have normal coagulation parameters (INR and PTT within normal range)

Who cannot join

  • Previous treatment with agents targeting on IGF pathway, phosphoinositide 3-kinase (PI3K) signaling pathway, protein kinase B (AKT), or mammalian target of rapamycin (mTOR) pathways
  • Prior treatment with exemestane (except adjuvant exemestane stopped >12 months prior to start of study treatment as long as the patient did not recur during or within 12 months after the end of adjuvant exemestane)
  • Known hypersensitivity to monoclonal antibody, mTOR inhibitors (e.g. sirolimus), or to the excipients of any study drugs
  • Ovarian suppression by ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist
  • Less than one week after receiving immunization with attenuated live vaccines prior to study treatment
  • Radiotherapy within 4 weeks prior to the start of the study treatment, except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to study treatment
Show all 21Show fewer
  • Chemotherapy, biological therapy (other than bevacizumab), immunotherapy or investigational agents within 5 half-life of the drug or within two weeks prior to the start of study treatment, whichever is longer; bevacizumab treatment within 4 weeks prior to start of study treatment (this criterion concerns anti-cancer therapy only)
  • Hormonal treatment for breast cancer within 2 weeks prior to start of study treatment
  • Major surgery in the judgement of the investigator within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study
  • Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use except Topical applications, inhaled sprays, eye drops or local injections or Patients on stable low dose of corticosteroids for at least two weeks before study entry
  • Chronic hepatitis B infection, chronic hepatitis C infection and/or known HIV carrier
  • QTcF prolongation > 470 ms or QT prolongation deemed clinically relevant by the investigator
  • Disease that is considered by the investigator to be rapidly progressing or life threatening such as extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor
  • History or current presence of brain or other CNS metastases
  • Bilateral diffuse lymphangitic carcinomatosis (in lung)
  • Hypokalemia of Grade >1
  • History of another primary malignancy within 5 years, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer
  • Family history of long QT syndrome
  • Any concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety and anti-tumor activity of the test drug(s)
  • Patients being treated with drugs recognized being strong or moderate CYP3A4 and/or PgP inhibitors and/or strong CYP3A4 inducers within 2 weeks prior to study entry
  • Patients received more than two lines of chemotherapy for locally advanced or metastatic breast cancer (For the Phase II: more than one line)

Trial locations and contacts

38 sites in 10 countries.

38 sites in 10 countries

Spain9 sites

  • Hospital Vall d'Hebron

    Barcelona, 08035

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Hospital Arnau de Vilanova

    Lleida, 25198

  • MD Anderson Cancer Center Madrid

    Madrid, 28033

  • Hospital Ramón y Cajal

    Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

  • Hospital Virgen del Rocío

    Seville, 41013

  • Hospital Clínico de Valencia

    Valencia, 46010

Other trials in Spain

Belgium8 sites

  • Brussels - UNIV UZ Brussel

    Brussels, 1090

  • Brussels - UNIV Saint-Luc

    Brussels, 1200

  • Charleroi - HOSP Grand Hôpital de Charleroi

    Charleroi, 6000

  • Edegem - UNIV UZ Antwerpen

    Edegem, 2650

  • UZ Leuven

    Leuven, 3000

  • Centre Hospitalier Universitaire de Liège

    Liège, 4000

  • Liège - HOSP St-Joseph

    Liège, 4000

  • CHU UCL Namur - Site De Sainte-Elisabeth

    Namur, 5000

Other trials in Belgium

France6 sites

  • HOP Jean Minjoz

    Besançon, 25030

  • INS Paoli-Calmettes

    Marseille, 13009

  • CTR Catherine de Sienne

    Nantes, 44202

  • HOP Européen G. Pompidou

    Paris, 75015

  • INS Curie

    Paris, 75248

  • Ctr Cario

    Plerin Sur Mer, 22190

Other trials in France

Taiwan4 sites

  • Kaohsiung Medical University Chung-Ho Memorial Hospital

    Kaohsiung City, 8807

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 112

Other trials in Taiwan

South Korea3 sites

  • National Cancer Center

    Goyang, 10408

  • Seoul National University Hospital

    Seoul, 110-744

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

United Kingdom3 sites

  • Ninewells Hospital & Medical School

    Dundee, DD1 9SY

  • St Bartholomew's Hospital

    London, EC1M 6BQ

  • Freeman Hospital

    Newcastle upon Tyne, NE7 7DN

Other trials in United Kingdom

Austria2 sites

  • Medical University of Graz State Hospital - University Hospital Graz

    Graz, 8036

  • Wilhelminenspital

    Vienna, 1160

Other trials in Austria

Ireland1 site

  • St. Vincent's University Hospital

    Dublin, D04 T6F4

Other trials in Ireland

Netherlands1 site

  • Maastricht University

    Maastricht, 6229 HX

Other trials in Netherlands

Sweden1 site

  • Centrummottagningen

    Stockholm, 171 76

Other trials in Sweden

About this study

Official title: A Phase Ib/II Randomized Study of BI 836845 in Combination With Exemestane and Everolimus Versus Exemestane and Everolimus Alone in Women With Locally Advanced or Metastatic Breast Cancer

Phase Ib / II study to determine the Maximum Tolerated Dose and Recommended Phase II Dose, and to evaluate the safety and antitumour activity, of BI 836845 and everolimus in combination with exemestane in women with HR+/HER2- advanced breast cancer

Conditions
Neoplasms
Being tested
Everolimus, Exemestane, BI 836845
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    10mg dose

  • ExemestaneDrug

    Fixed dose at 25mg

  • BI 836845Drug

    Also called xentuzumab

    1000 mg, recommended dose per Phase Ib part. Human monoclonal antibody. Dose escalation in Phase Ib. 2 dose levels (high or low) depending on the dose cohort explored

Study groups in NCT02123823
Study groupRoleWhat they receive
everolimus 10 mg + exemestane 25 mg - Phase IIActive comparatorSubjects received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
Receives: Drug: Everolimus; Drug: Exemestane
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase IIExperimentalSubjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal. Administration of xentuzumab was stopped after 28th October 2016, and participants in this group who remained in the trial could continue with everolimus 10 mg + exemestane 25 mg.
Receives: Drug: Everolimus; Drug: Exemestane; Drug: BI 836845
xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase IbExperimentalSubjects received a single dose of 750 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28- day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
Receives: Drug: Everolimus; Drug: Exemestane; Drug: BI 836845
xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase IbExperimentalSubjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal. Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
Receives: Drug: Everolimus; Drug: Exemestane; Drug: BI 836845

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival (PFS) - Phase II Part

    Progression-free survival (PFS) in the phase II part is presented. Progression-free survival (PFS) was defined as the time from randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause, whichever occurred earlier. Clinical disease progression was not considered for determination of a PFS event, unless the outcome of the progression was death. The cut-off date was 25th November 2016. At cut-off date, xentuzumab was discontinued in all patients in the experimental arm per sponsor decision, recruitment was also terminated. Patients who discontinued xentuzumab treatment continued with everolimus 10 mg + exemestane 25 mg treatment.

    Measured: From randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause or data cut-off (25Nov2016), up to 30 months.

  2. Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part

    Number of patients with dose limiting toxicity (DLT) in phase Ib part is presented.

    Measured: From first administration of study treatment until end of first treatment cycle, up to 28 days.

  3. Maximum Tolerated Dose (MTD) - Phase Ib Part

    The Maximum Tolerated Dose (MTD) in this study was defined as the highest dose level examined of trial medication, at which no more than 1 out of 6 patients experienced a DLT during the MTD evaluation period.

    The MTD evaluation period was defined as the time from the first administration of xentuzumab up to start of cycle 2.

    A "3+3" Phase Ib dose finding phase was performed to determine the MTD.

    Measured: up to 28 days.

Secondary outcomes (6)

  1. Number of Patients With Objective Response (OR) - Phase II Part

    Objective response (OR) - phase II part is presented. Objective response (OR), defined as best overall response of complete response (CR) or partial response (PR), where best overall response was determined according to RECIST 1.1 from date of randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.

    Measured: From randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy or data cut-off (25Nov2016), up to 30 months.

  2. Time to Progression (TTP) - Phase II Part

    Time to progression (TTP) is presented. Time to progression (TTP), defined as the time from the date of randomization until the date of the first objective tumour progression according to RECIST 1.1.

    Measured: From randomisation until the date of the first objective tumour progression according to RECIST 1.1. or data cut-off (25Nov2016), up to 30 months.

  3. Number of Patients With Disease Control (DC) - Phase II Part

    Disease control is defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) >= 24 weeks, or Non-CR/Non-PD for >= 24 weeks. PD=Progressive disease.

    Measured: From randomisation until data cut-off (25Nov2016), up to 30 months.

  4. Time to Objective Response - Phase II Part

    Time to objective response is presented. Time to objective response is defined as the time from randomisation until first documented complete response (CR) or partial response (PR).

    Measured: From randomisation until first documented complete response (CR) or partial response (PR) or data cut-off (25Nov2016), up to 30 months.

  5. Duration of Objective Response - Phase II Part

    Duration of objective response is presented. Duration of objective response is defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response (OR).

    Measured: From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months.

  6. Duration of Disease Control - Phase II Part

    Duration of disease control is presented. Duration of disease control is defined as the time from randomisation until the earliest of disease progression or death, among patients with disease control.

    Measured: From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2014 (estimated)
  2. Study start15 May 2014
  3. Primary completion25 Nov 2016
  4. Study completion14 Dec 2021

Resources

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
164 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02123823
Sponsor's protocol ID
1280.4
Other IDs
2013-001110-15
Status last verified
Jun 2025
First submitted
22 Apr 2014
Last updated
15 Jul 2025
Data monitoring committee
Yes
Individual data sharing
Yes: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.

Publications

  • Dercle L, McGale J, Zhao B, Schmitt J, Peltzer A, Schwartz LH, Amend M. Artificial intelligence and radiomics biomarkers for treatment response prediction in advanced HER2-negative breast cancer. Breast. 2025 Dec;84:104571. doi: 10.1016/j.breast.2025.104571. Epub 2025 Sep 3.

    PubMed 40974664

  • Schmid P, Sablin MP, Bergh J, Im SA, Lu YS, Martinez N, Neven P, Lee KS, Morales S, Perez-Fidalgo JA, Adamson D, Goncalves A, Prat A, Jerusalem G, Schlieker L, Espadero RM, Bogenrieder T, Huang DC, Crown J, Cortes J. A phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. Breast Cancer Res. 2021 Jan 15;23(1):8. doi: 10.1186/s13058-020-01382-8.

    PubMed 33451345

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Everolimus, Exemestane and BI 836845 in people with Neoplasms, run by Boehringer Ingelheim at 38 sites in 10 countries.

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 17 inclusion and 21 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: finished, as of the sponsor's last update on 15 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in Spain, Belgium, France, Taiwan, South Korea and 5 more countries. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) - Phase II Part (time frame: From randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause or data cut-off (25Nov2016), up to 30 months.). The study lists 3 primary outcomes in all. 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 NCT02123823, which also lists 2 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 15 Jul 2025.

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