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Breast NeoplasmsPhase 2NCT03659136

The XENERA™ 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread

A Phase 2 study testing Xentuzumab, Everolimus and Exemestane in people with Breast Neoplasms, run by Boehringer Ingelheim at 54 sites in 11 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

The main objective of the trial is to assess the efficacy of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
Xentuzumab, Everolimus and Exemestane
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
103 participants
Where
54 sitesin 11 countries
Study dates
28 Nov 2018to 11 May 2022
Phase
Phase 2
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 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented histologically confirmed breast cancer with ERand/ or PgR-positive and HER2-negative status
  • Locally advanced or metastatic breast cancer not deemed amenable to curative surgery or curative radiation therapy
  • Archival tumour sample available at the time of informed consent and provided to the central laboratory around the time of randomisation. Patients must provide a formalin-fixed paraffin embedded (FFPE) tissue biopsy sample preferably taken at the time of presentation with recurrent or metastatic disease (provision of a biopsy sample taken from the bone is not acceptable).
  • Patients must satisfy the following criteria for prior therapy:
  • Disease progression during treatment or within 12 months of completion of endocrine adjuvant therapy or
  • Disease progression while on or within 1 month after the end of prior endocrine therapy for advanced/metastatic breast cancer (Note: the endocrine therapy does not have to be the treatment immediately prior to trial entry).
Show all 13Show fewer
  • Patients must have
  • At least one measurable non-visceral lesion according to RECIST version 1.1 in either lymph nodes, soft tissue, skin and/or
  • At least one measurable non-visceral lesion according to RECIST version 1.1 as lytic or mixed (lytic + blastic) in bone and/or
  • At least one non-measurable (lytic, mixed lytic + blastic, or blastic) bone lesion according to RECIST version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  • Fasting glucose <8.9 mmol/L (<160 mg/dL) and HbA1c <8.0%
  • Adequate organ function

Who cannot join

  • Previous treatment with agents targeting the IGF pathway, AKT, or 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)
  • Evidence of visceral metastasis/es (i.e. liver, lung, peritoneal, pleural metastases, malignant pleural effusions, malignant peritoneal effusions) at screening. NOTE: Patients with a past history of visceral metastases are eligible if visceral metastases have completely resolved at least 3 months
  • History or evidence of metastatic disease to the brain
  • Leptomeningeal carcinomatosis
  • More than 1 prior line of chemotherapy for HR+ HER2- metastatic breast cancer
Show all 11Show fewer
  • Radiotherapy within 4 weeks prior to the start of study treatment
  • Use of concomitant systemic sex hormone therapy
  • History or presence of cardiovascular abnormalities
  • Known pre-existing interstitial lung disease
  • Further exclusion criteria apply

Trial locations and contacts

54 sites in 11 countries.

54 sites in 11 countries

United States16 sites

  • University Cancer and Blood Center

    Athens, Georgia, 30607

  • Beverly Hills Cancer Center

    Beverly Hills, California, 90211

  • Ironwood Cancer and Research Centers

    Chandler, Arizona, 85224

  • Florida Cancer Specialists

    Fort Myers, Florida, 33901

  • The Center for Cancer and Blood Disorders

    Fort Worth, Texas, 76104

  • Cancer Treatment Centers of America at Western Regional Medical Center

    Goodyear, Arizona, 85338

  • Hematology Oncology of Indiana

    Indianapolis, Indiana, 46260

  • HCA MidAmerica Division, Inc.

    Kansas City, Missouri, 64132

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203

  • Yale Cancer Center

    New Haven, Connecticut, 06510

  • Hematology Oncology Associates of Rockland

    Nyack, New York, 10960

  • Utah Cancer Specialists Cancer Center

    Salt Lake City, Utah, 84106

  • University of California San Francisco

    San Francisco, California, 94158

  • Northwest Medical Specialties, PLLC

    Tacoma, Washington, 98405

  • Southwestern Regional Medical Center

    Tulsa, Oklahoma, 74133

Other trials in United States

Spain10 sites

  • Hospital Teresa Herrera

    A Coruña, 15006

  • Hospital Clínic de Barcelona

    Barcelona, 08036

  • Hospital Arnau de Vilanova

    Lleida, 25198

  • Hospital General Universitario Gregorio Marañón

    Madrid, 28007

  • Hospital Ramón y Cajal

    Madrid, 28034

  • Hospital Clínico San Carlos

    Madrid, 28040

  • Hospital Regional Universitario de Málaga

    Málaga, 29010

  • Instituto Valenciano de Oncología

    Valencia, 46009

  • Clínica Quirón de Valencia

    Valencia, 46010

  • Hospital Clínico de Valencia

    Valencia, 46010

Other trials in Spain

France7 sites

  • INS Sainte Catherine

    Avignon, 84000

  • HOP Victor Hugo

    Le Mans, 72000

  • INS Paoli-Calmettes

    Marseille, 13009

  • INS Curie

    Paris, 75248

  • HOP Européen G. Pompidou

    Paris, 75908

  • HOP Lyon Sud

    Pierre-Bénite, 69495

  • INS Claudius Regaud IUCT-Oncopole

    Toulouse, 31059

Other trials in France

Greece5 sites

  • General Hospital of Athens "Alexandra"

    Athens, 11528

  • University General Hospital of Heraklion

    Heraklion, 71110

  • University Hospital of Larisa, Oncology Clinic

    Larissa, 41334

  • Metropolitan Hospital, Oncology Clinic

    Neo Faliro, Athens, 18547

  • Euromedica Kyanous Stavros General Hospital

    Thessaloniki, 54645

Other trials in Greece

Belgium4 sites

  • Brussels - UNIV Saint-Luc

    Brussels, 1200

  • Brussels - UNIV UZ Brussel

    Jette, 1090

  • Kortrijk - HOSP AZ Groeninge Kennedylaan

    Kortrijk, 8500

  • UZ Leuven

    Leuven, 3000

Other trials in Belgium

Italy3 sites

  • Istituto Nazionale IRCCS Tumori Fondazione Pascale

    Naples, 80131

  • Iov, Irccs

    Padova, 35128

  • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

    Roma, 00189

Other trials in Italy

Portugal3 sites

  • Fundação Champalimaud,

    Lisbon, 1400-038

  • Hospital Beatriz Ângelo

    Loures, 2674-514

  • Centro Hospitalar de Vila Nova de Gaia

    Vila Nova de Gaia, 4434-502

Other trials in Portugal

Australia2 sites

  • Peninsula Haematology & Oncology

    Frankston, Victoria, 3199

  • The Tweed Hospital

    Tweed Heads, New South Wales, 2485

Other trials in Australia

Germany2 sites

  • Universitätsklinikum Erlangen

    Erlangen, 91054

  • Vincentius-Diakonissen-Kliniken gAG

    Karlsruhe, 76135

Other trials in Germany

Canada1 site

  • CHU de Quebec-Universite Laval Research Centre

    Québec, G1S 4L8

Other trials in Canada

United Kingdom1 site

  • St Bartholomew's Hospital

    London, EC1A 7BE

Other trials in United Kingdom

About this study

Official title: XENERA™1: A Multi-centre, Double-blind, Placebo-controlled, Randomised Phase II Trial to Compare Efficacy of Xentuzumab in Combination With Everolimus and Exemestane Versus Everolimus and Exemestane in Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease

The main objective of the trial is to assess the efficacy of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease.

Being tested
Xentuzumab, Placebo, Everolimus, Exemestane
Medical subject headings
Breast Neoplasms

What participants receive

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

  • XentuzumabDrug

    Intravenous infusion

  • PlaceboDrug

    Intravenous infusion

  • EverolimusDrug

    Tablet

  • ExemestaneDrug

    Tablet

Study groups in NCT03659136
Study groupRoleWhat they receive
Xentuzumab/everolimus/exemestaneExperimentalNot described
Receives: Drug: Xentuzumab; Drug: Everolimus; Drug: Exemestane
Placebo/everolimus/exemestanePlacebo comparatorNot described
Receives: Drug: Placebo; Drug: Everolimus; Drug: Exemestane

What is being measured

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

  1. Progression Free Survival (PFS)

    Progression-free survival (PFS) defined as the time from randomisation until progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) in combination with modified MD Anderson Criteria (for bone lesion assessment), based on blinded independent assessment or death from any cause, whichever occurred earlier. As per RECIST, PD is defined as at least a 20% increase in the sum of diameters of target lesions, unequivocal progression of non-target lesions or the appearance of new lesions.

    Measured: From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.

Secondary outcomes (5)

  1. Overall Survival (OS)

    Overall survival (OS) defined as the time from randomisation until death from any cause. For patients with 'event' as an outcome for OS:

    OS[days] = date of outcome - date of randomisation + 1.

    For patients with 'censored' as an outcome for OS:

    OS (censored)[days] = date of outcome - date of randomisation + 1.

    Measured: From randomisation until death from any cause, up to 995 days.

  2. Number of Patients With Disease Control (DC)

    Disease control (DC) was defined as a best overall response (BOR) of either complete response (CR), partial response (PR), stable disease (SD) or Non-CR/No-PD. SD and Non-CR/Non-PR must have been observed up until at least week 24 tumor assessment. BOR was defined according to RECIST v1.1 in combination with modified MD Anderson Criteria (for bone lesion assessment) based on all evaluable tumor assessments from randomisation until the earliest of PD, start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent or death. To be aligned with the primary endpoint derivation, tumor assessments after two or more consecutively misses assessments were not considered. DC was assessed by independent reviewers.

    Measured: From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.

  3. Duration of Disease Control (DC)

    Duration of disease control (DC), defined as the time from randomisation until the earliest of disease progression (according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) in combination with modified MD Anderson Criteria (for bone lesion assessment) or death from any cause, among patients with DC. Duration of DC was assessed by independent reviewers.

    The duration of DC was calculated as followed:

    For patients with disease progression or death:

    Duration of DC [days] = date of outcome - date of randomisation + 1

    For patients without disease progression or death:

    Duration of DC (censored) [days] = date of outcome - date of randomisation + 1

    Measured: From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.

  4. Number of Participants With Objective Response (OR)

    Number of participants with objective response (OR) by independent assessment. OR is defined as a best overall response of complete response (CR) or partial response (PR). Best overall response is defined according to RECIST v1.1 in combination with modified MD Anderson Criteria (for bone lesion assessment) and will consider all tumor assessments from randomisation until the earliest of PD, start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent or death. To be aligned with the primary endpoint derivation, tumor assessments after two or more consecutively misses assessments were not considered.

    Measured: From randomisation until end of treatment, up to 892 days.

  5. Time to Pain Progression or Intensification of Pain Palliation

    Time to pain progression or intensification of pain palliation was defined as the time from randomisation until the earliest of:

    • 2 point increase from baseline in the Brief Pain Inventory - Short Form (BPI-SF), Item 3 (worst pain), without a decrease (of ≥1 point) from baseline analgesics use (via the 8-point Analgesic Quantification Algorithm [AQA]), or
    • 2 point increase from baseline in the AQA, or Death.

    Measured: From randomisation until the earliest of pain progression, intensification of pain palliation, death or the time point of progression free survival analysis, up to 843 days.

Timeline

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

  1. First posted6 Sep 2018
  2. Study start28 Nov 2018
  3. Primary completion30 Aug 2021
  4. Study completion11 May 2022

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03659136
Sponsor's protocol ID
1280-0022
Other IDs
2017-003131-11, 2017
Status last verified
Feb 2025
First submitted
3 Sep 2018
Last updated
24 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency

Publications

  • Schmid P, Cortes J, Joaquim A, Janez NM, Morales S, Diaz-Redondo T, Blau S, Neven P, Lemieux J, Garcia-Saenz JA, Hart L, Biyukov T, Baktash N, Massey D, Burris HA 3rd, Rugo HS. XENERA-1: a randomised double-blind Phase II trial of xentuzumab in combination with everolimus and exemestane versus everolimus and exemestane in patients with hormone receptor-positive/HER2-negative metastatic breast cancer and non-visceral disease. Breast Cancer Res. 2023 Jun 12;25(1):67. doi: 10.1186/s13058-023-01649-w.

    PubMed 37308971

  • 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 2 study testing Xentuzumab, Everolimus and Exemestane in people with Breast Neoplasms, run by Boehringer Ingelheim at 54 sites in 11 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 13 inclusion and 11 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 24 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States, Spain, France, Greece, Belgium and 6 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 29 Sep 2022). 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) (time frame: From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.). 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 NCT03659136, 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 24 Feb 2025.

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