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
- Conditions
- Breast Neoplasms
- Interventions
- Registration Number
- NCT03659136
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 103
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Documented histologically confirmed breast cancer with ERand/ or PgR-positive and HER2-negative status
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Locally advanced or metastatic breast cancer not deemed amenable to curative surgery or curative radiation therapy
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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).
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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.
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Fasting glucose <8.9 mmol/L (<160 mg/dL) and HbA1c <8.0%
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Adequate organ function
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo/everolimus/exemestane Placebo - Placebo/everolimus/exemestane Exemestane - Xentuzumab/everolimus/exemestane Everolimus - Xentuzumab/everolimus/exemestane Exemestane - Placebo/everolimus/exemestane Everolimus - Xentuzumab/everolimus/exemestane Xentuzumab -
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days. 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) From randomisation until death from any cause, up to 995 days. 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.Number of Patients With Disease Control (DC) From randomisation until the earliest of progressive disease or death from any cause, up to 892 days. 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.
Duration of Disease Control (DC) From randomisation until the earliest of progressive disease or death from any cause, up to 892 days. 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 + 1Number of Participants With Objective Response (OR) From randomisation until end of treatment, up to 892 days. 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.
Time to Pain Progression or Intensification of Pain Palliation 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. 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.
Trial Locations
- Locations (54)
Brussels - UNIV Saint-Luc
🇧🇪Bruxelles, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Cancer Treatment Centers of America at Western Regional Medical Center
🇺🇸Goodyear, Arizona, United States
University Cancer and Blood Center
🇺🇸Athens, Georgia, United States
INS Sainte Catherine
🇫🇷Avignon, France
Peninsula Haematology & Oncology
🇦🇺Frankston, Victoria, Australia
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Hospital Arnau de Vilanova
🇪🇸Lleida, Spain
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Iov, Irccs
🇮🇹Padova, Italy
Hematology Oncology Associates of Rockland
🇺🇸Nyack, New York, United States
CHU de Quebec-Universite Laval Research Centre
🇨🇦Quebec, Canada
University General Hospital of Heraklion
🇬🇷Heraklion, Greece
HCA MidAmerica Division, Inc.
🇺🇸Kansas City, Missouri, United States
Ironwood Cancer and Research Centers
🇺🇸Chandler, Arizona, United States
St Bartholomew's Hospital
🇬🇧London, United Kingdom
HOP Victor Hugo
🇫🇷Le Mans, France
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Fundação Champalimaud,
🇵🇹Lisboa, Portugal
Kortrijk - HOSP AZ Groeninge Kennedylaan
🇧🇪Kortrijk, Belgium
Hospital Ramón y Cajal
🇪🇸Madrid, Spain
Clínica Quirón de Valencia
🇪🇸Valencia, Spain
Hospital Regional Universitario de Málaga
🇪🇸Málaga, Spain
General Hospital of Athens "Alexandra"
🇬🇷Athens, Greece
Metropolitan Hospital, Oncology Clinic
🇬🇷Neo Faliro, Athens, Greece
Southwestern Regional Medical Center
🇺🇸Tulsa, Oklahoma, United States
Brussels - UNIV UZ Brussel
🇧🇪Jette, Belgium
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital Clínico de Valencia
🇪🇸Valencia, Spain
The Center for Cancer and Blood Disorders
🇺🇸Fort Worth, Texas, United States
Euromedica Kyanous Stavros General Hospital
🇬🇷Thessaloniki, Greece
Centro Hospitalar de Vila Nova de Gaia
🇵🇹Vila Nova de Gaia, Portugal
INS Claudius Regaud IUCT-Oncopole
🇫🇷Toulouse, France
Hospital Clínico San Carlos
🇪🇸Madrid, Spain
Vincentius-Diakonissen-Kliniken gAG
🇩🇪Karlsruhe, Germany
University Hospital of Larisa, Oncology Clinic
🇬🇷Larisa, Greece
Hematology Oncology of Indiana
🇺🇸Indianapolis, Indiana, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Tennessee Oncology, PLLC
🇺🇸Nashville, Tennessee, United States
Utah Cancer Specialists Cancer Center
🇺🇸Salt Lake City, Utah, United States
Hospital Beatriz Ângelo
🇵🇹Loures, Portugal
Istituto Nazionale IRCCS Tumori Fondazione Pascale
🇮🇹Napoli, Italy
HOP Lyon Sud
🇫🇷Pierre Benite, France
Universitätsklinikum Erlangen
🇩🇪Erlangen, Germany
HOP Européen G. Pompidou
🇫🇷Paris, France
Florida Cancer Specialists
🇺🇸Fort Myers, Florida, United States
The Tweed Hospital
🇦🇺Tweed Heads, New South Wales, Australia
INS Curie
🇫🇷Paris, France
INS Paoli-Calmettes
🇫🇷Marseille, France
Hospital Teresa Herrera
🇪🇸A Coruña, Spain
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
🇮🇹Roma, Italy