Clinical trial NCT03659136: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2018-09-06
Enrollment: 103
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomisation until death from any cause, up to 995 days.
measure: Number of Patients With Disease Control (DC)
timeFrame: From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.
measure: Duration of Disease Control (DC)
timeFrame: From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.
measure: Number of Participants With Objective Response (OR)
timeFrame: From randomisation until end of treatment, up to 892 days.
measure: Time to Pain Progression or Intensification of Pain Palliation
timeFrame: 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.
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: Goodyear
country: United States
facility: Cancer Treatment Centers of America at Western Regional Medical Center
state: Arizona
city: Beverly Hills
country: United States
facility: Beverly Hills Cancer Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Athens
country: United States
facility: University Cancer and Blood Center
state: Georgia
city: Indianapolis
country: United States
facility: Hematology Oncology of Indiana
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: HCA MidAmerica Division, Inc.
state: Missouri
city: Nyack
country: United States
facility: Hematology Oncology Associates of Rockland
state: New York
city: Tulsa
country: United States
facility: Southwestern Regional Medical Center
state: Oklahoma
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Fort Worth
country: United States
facility: The Center for Cancer and Blood Disorders
state: Texas
city: Salt Lake City
country: United States
facility: Utah Cancer Specialists Cancer Center
state: Utah
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Tweed Heads
country: Australia
facility: The Tweed Hospital
state: New South Wales
city: Frankston
country: Australia
facility: Peninsula Haematology & Oncology
state: Victoria
city: Bruxelles
country: Belgium
facility: Brussels - UNIV Saint-Luc
city: Jette
country: Belgium
facility: Brussels - UNIV UZ Brussel
city: Kortrijk
country: Belgium
facility: Kortrijk - HOSP AZ Groeninge Kennedylaan
city: Leuven
country: Belgium
facility: UZ Leuven
city: Quebec
country: Canada
facility: CHU de Quebec-Universite Laval Research Centre
city: Avignon
country: France
facility: INS Sainte Catherine
city: Le Mans
country: France
facility: HOP Victor Hugo
city: Marseille
country: France
facility: INS Paoli-Calmettes
city: Paris
country: France
facility: INS Curie
city: Paris
country: France
facility: HOP Européen G. Pompidou
city: Pierre Benite
country: France
facility: HOP Lyon Sud
city: Toulouse
country: France
facility: INS Claudius Regaud IUCT-Oncopole
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
city: Karlsruhe
country: Germany
facility: Vincentius-Diakonissen-Kliniken gAG
city: Athens
country: Greece
facility: General Hospital of Athens "Alexandra"
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Larisa
country: Greece
facility: University Hospital of Larisa, Oncology Clinic
city: Neo Faliro, Athens
country: Greece
facility: Metropolitan Hospital, Oncology Clinic
city: Thessaloniki
country: Greece
facility: Euromedica Kyanous Stavros General Hospital
city: Napoli
country: Italy
facility: Istituto Nazionale IRCCS Tumori Fondazione Pascale
city: Padova
country: Italy
facility: Iov, Irccs
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
city: Lisboa
country: Portugal
facility: Fundação Champalimaud,
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: A Coruña
country: Spain
facility: Hospital Teresa Herrera
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Clínica Quirón de Valencia
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
Study officials:
References:
citation: 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.