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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: Placebo; Drug: Xentuzumab; Drug: Everolimus; Drug: Exemestane

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Tweed Heads, New South Wales, Australia, 2485
      • The Tweed Hospital
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Peninsula Haematology & Oncology
• Belgium
  • Bruxelles, Belgium, 1200
    • Brussels - UNIV Saint-Luc
  • Jette, Belgium, 1090
    • Brussels - UNIV UZ Brussel
  • Kortrijk, Belgium, 8500
    • Kortrijk - HOSP AZ Groeninge Kennedylaan
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Quebec, Canada, G1S 4L8
    • CHU de Quebec-Universite Laval Research Centre
• France
  • Avignon, France, 84000
    • INS Sainte Catherine
  • Le Mans, France, 72000
    • HOP Victor Hugo
  • Marseille, France, 13009
    • INS Paoli-Calmettes
  • Paris, France, 75908
    • HOP Européen G. Pompidou
  • Paris, France, 75248
    • INS Curie
  • Pierre Benite, France, 69495
    • HOP Lyon Sud
  • Toulouse, France, 31059
    • INS Claudius Regaud IUCT-Oncopole
• Germany
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
  • Karlsruhe, Germany, 76135
    • Vincentius-Diakonissen-Kliniken gAG
• Greece
  • Athens, Greece, 11528
    • General Hospital of Athens "Alexandra"
  • Heraklion, Greece, 71110
    • University General Hospital of Heraklion
  • Larisa, Greece, 41334
    • University Hospital of Larisa, Oncology Clinic
  • Neo Faliro, Athens, Greece, 18547
    • Metropolitan Hospital, Oncology Clinic
  • Thessaloniki, Greece, 54645
    • Euromedica Kyanous Stavros General Hospital
• Italy
  • Napoli, Italy, 80131
    • Istituto Nazionale IRCCS Tumori Fondazione Pascale
  • Padova, Italy, 35128
    • Iov, Irccs
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
• Portugal
  • Lisboa, Portugal, 1400-038
    • Fundação Champalimaud,
  • Loures, Portugal, 2674-514
    • Hospital Beatriz Angelo
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Lleida, Spain, 25198
    • Hospital Arnau de Vilanova
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28034
    • Hospital Ramón y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
  • Valencia, Spain, 46010
    • Clínica Quirón de Valencia
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew's Hospital
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Ironwood Cancer and Research Centers
    • Goodyear, Arizona, United States, 85338
      • Cancer Treatment Centers of America at Western Regional Medical Center
  • California
    • Beverly Hills, California, United States, 90211
      • Beverly Hills Cancer Center
    • San Francisco, California, United States, 94158
      • University of California San Francisco
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Hematology Oncology Of Indiana
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA MidAmerica Division, Inc.
  • New York
    • Nyack, New York, United States, 10960
      • Hematology Oncology Associates of Rockland
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74133
      • Southwestern Regional Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Texas
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer and Blood Disorders
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists Cancer Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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
• Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Xentuzumab/everolimus/exemestane	Drug: Xentuzumab; Intravenous infusion; Drug: Everolimus; Tablet; Drug: Exemestane; Tablet
Placebo Comparator: Placebo/everolimus/exemestane	Drug: Placebo; Intravenous infusion; Drug: Everolimus; Tablet; Drug: Exemestane; Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.
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	From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.
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.	From randomisation until end of treatment, up to 892 days.
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.	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.
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.	From randomisation until death from any cause, up to 995 days.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• 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.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2018
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): May 11, 2022

Study Registration Dates

• First Submitted: September 3, 2018
• First Submitted That Met QC Criteria: September 3, 2018
• First Posted (Actual): September 6, 2018

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Hormones, Hormone Substitutes, and Hormone Antagonists; Protein Kinase Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; MTOR Inhibitors; Everolimus; Exemestane
• Other Study ID Numbers: 1280-0022; 2017-003131-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

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, except for the following exclusions:

1. studies in products where Boehringer Ingelheim is not the license holder;
2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datasharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No