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

Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03659136
• Other study ID #: 1280-0022
• Secondary ID: 2017-003131-11
• Status: Completed
• Phase: Phase 2
• Start date: November 28, 2018
• Est. completion date: May 11, 2022

Study information

• Verified date: May 2023
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 103
• Est. completion date: May 11, 2022
• Est. primary completion date: August 30, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• Xentuzumab
Intravenous infusion
• Placebo
Intravenous infusion
• Everolimus
Tablet
• Exemestane
Tablet

Locations

Country	Name	City	State
Australia	Peninsula Haematology & Oncology	Frankston	Victoria
Australia	The Tweed Hospital	Tweed Heads	New South Wales
Belgium	Brussels - UNIV Saint-Luc	Bruxelles
Belgium	Brussels - UNIV UZ Brussel	Jette
Belgium	Kortrijk - HOSP AZ Groeninge Kennedylaan	Kortrijk
Belgium	UZ Leuven	Leuven
Canada	CHU de Quebec-Universite Laval Research Centre	Quebec
France	INS Sainte Catherine	Avignon
France	HOP Victor Hugo	Le Mans
France	INS Paoli-Calmettes	Marseille
France	HOP Européen G. Pompidou	Paris
France	INS Curie	Paris
France	HOP Lyon Sud	Pierre Benite
France	INS Claudius Regaud IUCT-Oncopole	Toulouse
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Vincentius-Diakonissen-Kliniken gAG	Karlsruhe
Greece	General Hospital of Athens "Alexandra"	Athens
Greece	University General Hospital of Heraklion	Heraklion
Greece	University Hospital of Larisa, Oncology Clinic	Larisa
Greece	Metropolitan Hospital, Oncology Clinic	Neo Faliro, Athens
Greece	Euromedica Kyanous Stavros General Hospital	Thessaloniki
Italy	Istituto Nazionale IRCCS Tumori Fondazione Pascale	Napoli
Italy	Iov, Irccs	Padova
Italy	Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza	Roma
Portugal	Fundação Champalimaud,	Lisboa
Portugal	Hospital Beatriz Ângelo	Loures
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Spain	Hospital Teresa Herrera	A Coruña
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Arnau de Vilanova	Lleida
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Regional Universitario de Málaga	Málaga
Spain	Clínica Quirón de Valencia	Valencia
Spain	Hospital Clínico de Valencia	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
United Kingdom	St Bartholomew's Hospital	London
United States	University Cancer and Blood Center	Athens	Georgia
United States	Beverly Hills Cancer Center	Beverly Hills	California
United States	Ironwood Cancer and Research Centers	Chandler	Arizona
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Cancer Treatment Centers of America at Western Regional Medical Center	Goodyear	Arizona
United States	Hematology Oncology of Indiana	Indianapolis	Indiana
United States	HCA MidAmerica Division, Inc.	Kansas City	Missouri
United States	University of Minnesota	Minneapolis	Minnesota
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Hematology Oncology Associates of Rockland	Nyack	New York
United States	Utah Cancer Specialists Cancer Center	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Southwestern Regional Medical Center	Tulsa	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

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