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

NCT ID: NCT03659136

Last Updated: 2025-02-24

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

103 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-28

Study Completion Date

2022-05-11

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Xentuzumab/everolimus/exemestane

Group Type EXPERIMENTAL

Xentuzumab

Intervention Type DRUG

Intravenous infusion

Everolimus

Intervention Type DRUG

Tablet

Exemestane

Intervention Type DRUG

Tablet

Placebo/everolimus/exemestane

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Intravenous infusion

Everolimus

Intervention Type DRUG

Tablet

Exemestane

Intervention Type DRUG

Tablet

Interventions

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Xentuzumab

Intravenous infusion

Intervention Type DRUG

Placebo

Intravenous infusion

Intervention Type DRUG

Everolimus

Tablet

Intervention Type DRUG

Exemestane

Tablet

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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).
* 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

Exclusion Criteria

* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Ironwood Cancer and Research Centers

Chandler, Arizona, United States

Site Status

Cancer Treatment Centers of America at Western Regional Medical Center

Goodyear, Arizona, United States

Site Status

Beverly Hills Cancer Center

Beverly Hills, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

Yale Cancer Center

New Haven, Connecticut, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

University Cancer and Blood Center

Athens, Georgia, United States

Site Status

Hematology Oncology of Indiana

Indianapolis, Indiana, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

HCA MidAmerica Division, Inc.

Kansas City, Missouri, United States

Site Status

Hematology Oncology Associates of Rockland

Nyack, New York, United States

Site Status

Southwestern Regional Medical Center

Tulsa, Oklahoma, United States

Site Status

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Site Status

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Site Status

Utah Cancer Specialists Cancer Center

Salt Lake City, Utah, United States

Site Status

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

Site Status

The Tweed Hospital

Tweed Heads, New South Wales, Australia

Site Status

Peninsula Haematology & Oncology

Frankston, Victoria, Australia

Site Status

Brussels - UNIV Saint-Luc

Brussels, , Belgium

Site Status

Brussels - UNIV UZ Brussel

Jette, , Belgium

Site Status

Kortrijk - HOSP AZ Groeninge Kennedylaan

Kortrijk, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

CHU de Quebec-Universite Laval Research Centre

Québec, , Canada

Site Status

INS Sainte Catherine

Avignon, , France

Site Status

HOP Victor Hugo

Le Mans, , France

Site Status

INS Paoli-Calmettes

Marseille, , France

Site Status

INS Curie

Paris, , France

Site Status

HOP Européen G. Pompidou

Paris, , France

Site Status

HOP Lyon Sud

Pierre-Bénite, , France

Site Status

INS Claudius Regaud IUCT-Oncopole

Toulouse, , France

Site Status

Universitätsklinikum Erlangen

Erlangen, , Germany

Site Status

Vincentius-Diakonissen-Kliniken gAG

Karlsruhe, , Germany

Site Status

General Hospital of Athens "Alexandra"

Athens, , Greece

Site Status

University General Hospital of Heraklion

Heraklion, , Greece

Site Status

University Hospital of Larisa, Oncology Clinic

Larissa, , Greece

Site Status

Metropolitan Hospital, Oncology Clinic

Neo Faliro, Athens, , Greece

Site Status

Euromedica Kyanous Stavros General Hospital

Thessaloniki, , Greece

Site Status

Istituto Nazionale IRCCS Tumori Fondazione Pascale

Napoli, , Italy

Site Status

Iov, Irccs

Padua, , Italy

Site Status

Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

Roma, , Italy

Site Status

Fundação Champalimaud,

Lisbon, , Portugal

Site Status

Hospital Beatriz Ângelo

Loures, , Portugal

Site Status

Centro Hospitalar de Vila Nova de Gaia

Vila Nova de Gaia, , Portugal

Site Status

Hospital Teresa Herrera

A Coruña, , Spain

Site Status

Hospital Clínic de Barcelona

Barcelona, , Spain

Site Status

Hospital Arnau de Vilanova

Lleida, , Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

Site Status

Hospital Ramón y Cajal

Madrid, , Spain

Site Status

Hospital Clínico San Carlos

Madrid, , Spain

Site Status

Hospital Regional Universitario de Málaga

Málaga, , Spain

Site Status

Instituto Valenciano de Oncología

Valencia, , Spain

Site Status

Clínica Quirón de Valencia

Valencia, , Spain

Site Status

Hospital Clínico de Valencia

Valencia, , Spain

Site Status

St Bartholomew's Hospital

London, , United Kingdom

Site Status

Countries

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United States Australia Belgium Canada France Germany Greece Italy Portugal Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 37308971 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33451345 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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2017-003131-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1280-0022

Identifier Type: -

Identifier Source: org_study_id

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