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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03659136




Registration number
NCT03659136
Ethics application status
Date submitted
3/09/2018
Date registered
6/09/2018
Date last updated
6/08/2019

Titles & IDs
Public title
The XENERA™-1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Post-menopausal Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread
Scientific 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 Post-menopausal Women With HR+ / HER2- Metastatic Breast Cancer and Non-visceral Disease
Secondary ID [1] 0 0
2017-003131-11
Secondary ID [2] 0 0
1280-0022
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Xentuzumab
Treatment: Drugs - Placebo
Treatment: Drugs - Everolimus
Treatment: Drugs - Exemestane

Experimental: Xentuzumab/everolimus/exemestane -

Placebo Comparator: Placebo/everolimus/exemestane -


Treatment: Drugs: Xentuzumab
Intravenous infusion

Treatment: Drugs: Placebo
Intravenous infusion

Treatment: Drugs: Everolimus
Tablet

Treatment: Drugs: Exemestane
Tablet

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression free survival (PFS) as assessed by central review - Defined as time from randomisation until disease progression according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) or death from any cause, whichever occurs earlier
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Overall survival (OS) defined as the time from randomisation until death from any cause - Defined as the time from randomisation until death from any cause
Timepoint [1] 0 0
Up to 3 years
Secondary outcome [2] 0 0
Disease control (DC) - Defined as a best overall response of complete response (CR), partial response (PR), stable disease (SD) or Non-CR/Non-Progressive Disease (Non- CR/Non-PD). SD and Non-CR/Non PD must have a minimum duration of 24 weeks from randomisation. Best overall response is defined according to RECIST version 1.1 and will consider all tumour assessments from randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anticancer therapy, loss to follow-up or withdrawal of consent
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
Duration of DC is defined as the time from randomisation until the earliest of disease progression or death, among patients with DC - Defined as the time from randomisation until the earliest of disease progression or death, among patients with DC
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Objective response (OR) Defined as a best overall response of complete response (CR) or partial response (PR) - Defined as a best overall response of CR or PR. Best overall response is defined according to RECIST version 1.1 and will consider all tumour assessments from randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy, loss to follow-up or withdrawal of consent
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Time to pain progression or intensification of pain palliation - Defined as the time from randomisation until the earliest of a clinically significant increase in pain (=2-point increase from baseline in the Brief Pain Inventory- Short Form [BPI-SF] Item 3) without a decrease in analgesics use, or intensification in pain palliation (=2-point increase in the 8-point Analgesic Quantification Algorithm [AQA]), or death
Timepoint [5] 0 0
Up to 24 months

Eligibility
Key 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:

- Progressed during treatment or within 12 months of completion of adjuvant therapy
with an aromatase inhibitor and/or tamoxifen if post-menopausal, or tamoxifen if
pre or peri-menopausal or

- Progressed while on or within 1 month after the end of prior aromatase inhibitor
therapy for advanced/metastatic breast cancer if post-menopausal, or prior
endocrine treatment for advanced/metastatic breast cancer if pre- or
peri-menopausal.

- Patients must not have received more than one previous line of non-steroidal aromatase
inhibitor treatment for advanced/metastatic disease. Prior treatment with one line of
CDK4/6 inhibitors is allowed.

- Prior treatment with fulvestrant if duration was at least 2 years in the adjuvant
setting or at least 6 months in the metastatic setting is allowed.

- Patients must be post-menopausal at time of signature of trial informed consent.

- 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 or mixed (lytic + blastic) bone lesion
according to RECIST version 1.1

- Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.

- Adequate organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Previous treatment with agents targeting the IGF pathway, PI3K, 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)

- History or evidence of metastatic disease to the brain

- Leptomeningeal carcinomatosis

- Any previous 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
The Tweed Hospital - Tweed Heads
Recruitment hospital [2] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [3] 0 0
Peninsula Haematology & Oncology - Frankston
Recruitment postcode(s) [1] 0 0
2485 - Tweed Heads
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
North Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
Belgium
State/province [17] 0 0
Brussel
Country [18] 0 0
Belgium
State/province [18] 0 0
Bruxelles
Country [19] 0 0
Belgium
State/province [19] 0 0
Kortrijk
Country [20] 0 0
Belgium
State/province [20] 0 0
Leuven
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
France
State/province [22] 0 0
Bordeaux
Country [23] 0 0
France
State/province [23] 0 0
Le Mans
Country [24] 0 0
France
State/province [24] 0 0
Marseille
Country [25] 0 0
France
State/province [25] 0 0
Paris
Country [26] 0 0
France
State/province [26] 0 0
Pierre Benite
Country [27] 0 0
Germany
State/province [27] 0 0
Erlangen
Country [28] 0 0
Germany
State/province [28] 0 0
Heidelberg
Country [29] 0 0
Germany
State/province [29] 0 0
Karlsruhe
Country [30] 0 0
Germany
State/province [30] 0 0
Köln
Country [31] 0 0
Germany
State/province [31] 0 0
Tübingen
Country [32] 0 0
Greece
State/province [32] 0 0
Heraklion
Country [33] 0 0
Greece
State/province [33] 0 0
Larisa
Country [34] 0 0
Greece
State/province [34] 0 0
Neo Faliro, Athens
Country [35] 0 0
Greece
State/province [35] 0 0
Thessaloniki
Country [36] 0 0
Italy
State/province [36] 0 0
Padova
Country [37] 0 0
Italy
State/province [37] 0 0
Roma
Country [38] 0 0
Portugal
State/province [38] 0 0
Braga
Country [39] 0 0
Portugal
State/province [39] 0 0
Lisboa
Country [40] 0 0
Portugal
State/province [40] 0 0
Loures
Country [41] 0 0
Portugal
State/province [41] 0 0
Matosinhos
Country [42] 0 0
Portugal
State/province [42] 0 0
Porto
Country [43] 0 0
Portugal
State/province [43] 0 0
Vila Nova de Gaia
Country [44] 0 0
Spain
State/province [44] 0 0
A Coruña
Country [45] 0 0
Spain
State/province [45] 0 0
Barcelona
Country [46] 0 0
Spain
State/province [46] 0 0
Madrid
Country [47] 0 0
Spain
State/province [47] 0 0
Málaga
Country [48] 0 0
Spain
State/province [48] 0 0
Valencia
Country [49] 0 0
United Kingdom
State/province [49] 0 0
Nottingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The main objective of the trial is to assess the anti-tumor activity of xentuzumab in
combination with everolimus and exemestane over everolimus and exemestane in post menopausal
patients with HR+/ HER2- advanced or metastatic breast cancer and non-visceral disease.
Trial website
https://clinicaltrials.gov/show/NCT03659136
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Boehringer Ingelheim
Address 0 0
Country 0 0
Phone 0 0
1-800-243-0127
Fax 0 0
Email 0 0
clintriage.rdg@boehringer-ingelheim.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03659136