Clinical trial • Phase III • Oncology
DENOSUMAB for Breast cancer | BRCA1 gene mutation
Phase III trial of DENOSUMAB for Breast cancer | BRCA1 gene mutation.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- Breast cancer | BRCA1 gene mutation
- Trial Stage
- Phase III
- Drug Modality
- Monoclonal antibody
Key dates
- Initial CTIS Submission Date
- 04-07-2024
- First CTIS Authorization Date
- 14-08-2024
Trial design
Randomised, placebo ("identical to the test product") matching the test product; test product: xgeva 120 mg solution for injection (denosumab), subcutaneous. exact schedule not explicitly stated in the ctis record.-controlled Phase III trial in Austria, Spain, Germany.
- Randomised
- Yes
- Comparator
- Placebo ("Identical to the Test product") matching the test product; Test product: XGEVA 120 mg solution for injection (denosumab), subcutaneous. Exact schedule not explicitly stated in the CTIS record.
- Target Sample Size
- 1768
Eligibility
Recruits 1768 Vulnerable population selected (isVulnerablePopulationSelected = true). Participants are adult women (age 25–55) so consent is obtained from the participant. "Written informed consent before any study-specific procedure is performed" is required. No assent procedures for minors are applicable because minors are excluded..
- Pregnancy Exclusion
- Pregnant or lactating women (within the last 2 months prior to randomization)
- Vulnerable Population
- Vulnerable population selected (isVulnerablePopulationSelected = true). Participants are adult women (age 25–55) so consent is obtained from the participant. "Written informed consent before any study-specific procedure is performed" is required. No assent procedures for minors are applicable because minors are excluded.
Inclusion criteria
- {"criterion_text":"- Women with a confirmed deleterious or likely deleterious BRCA 1 germline mutation (Variant class 4 or 5)"}
- {"criterion_text":"- Age ≥ 25 years and ≤ 55 years at randomization"}
- {"criterion_text":"- No evidence of breast cancer by MRI or MG and clinical breast examination within the last 6 months prior to randomization"}
- {"criterion_text":"- No clinical evidence of ovarian cancer at randomization"}
- {"criterion_text":"- Negative pregnancy test at randomization for women of childbearing potential"}
- {"criterion_text":"- No preventive breast surgery planned at time of randomization"}
- {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1"}
- {"criterion_text":"- Written informed consent before any study-specific procedure is performed"}
Exclusion criteria
- {"criterion_text":"- Prior bilateral mastectomy"}
- {"criterion_text":"- Participant has a known prior history or current evidence of osteonecrosis or osteomyelitis of the jaw, or an active dental/jaw condition which requires oral surgery including tooth extraction ≤ 3 months prior enrollment"}
- {"criterion_text":"- Concurrent treatment with a bisphosphonate or an anti-angiogenic agent"}
- {"criterion_text":"- Concurrent therapy with other Investigational Products"}
- {"criterion_text":"- Any major medical or psychiatric condition that may prevent the participant from completing the study"}
- {"criterion_text":"- Known active infection with Hepatitis B virus or Hepatitis C virus"}
- {"criterion_text":"- Known infection with human immunodeficiency virus (HIV)"}
- {"criterion_text":"- Hypersensitivity to the active substance or to any of the excipients"}
- {"criterion_text":"- Known rare hereditary problems of fructose intolerance"}
- {"criterion_text":"- History of ovarian cancer (including fallopian tube and primary peritoneal cancer)"}
- {"criterion_text":"- History of breast cancer"}
- {"criterion_text":"- History of invasive cancer except for basal cell or squamous cell skin cancer. History of the following are also allowed: carcinoma in situ of the cervix, stage 1 papillary or follicular thyroid cancer, atypical hyperplasia or LCIS (Lobular Carcinoma In Situ)"}
- {"criterion_text":"- Pregnant or lactating women (within the last 2 months prior to randomization)"}
- {"criterion_text":"- Unwillingness to use highly effective contraception method during and within at least 5 months after cessation of denosumab/placebo therapy in women of childbearing potential"}
- {"criterion_text":"- Clinically relevant hypocalcaemia (history and current condition), or serum calcium <2.0 mmol/L (<8.0 mg/dL) or corrected calcium (<2.1 mmol/L) Hypocalcemia defined by calcium below the normal range (a single value below the normal range does not necessarily constitute hypocalcemia, but should be 'corrected' before dosing the participant). Monitoring of calcium level in regular intervals (usually prior to IP administration) is highly recommended"}
- {"criterion_text":"- Tamoxifen, raloxifene or aromatase inhibitor use during the last 3 months prior to randomization or for a duration of more than 3 years in total (current and prior HRT is permitted)"}
- {"criterion_text":"- Any prior use of denosumab"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Time to the occurrence of any breast cancer (invasive or DCIS)","definition_or_measurement_approach":"Time-to-event endpoint measuring time from randomization to occurrence/diagnosis of any breast cancer (invasive or DCIS)."}
Secondary endpoints
- {"endpoint_text":"- Time to invasive breast cancer","definition_or_measurement_approach":"Time-to-event (time from randomization to diagnosis of invasive breast cancer)."}
- {"endpoint_text":"- Time to invasive triple negative breast cancer","definition_or_measurement_approach":"Time-to-event (time from randomization to diagnosis of invasive triple negative breast cancer)."}
- {"endpoint_text":"- Time to ovarian, fallopian tube or primary peritoneal cancer (in women who have not undergone PBSO)","definition_or_measurement_approach":"Time-to-event (time from randomization to diagnosis of ovarian/fallopian tube/primary peritoneal cancer in women without PBSO)."}
- {"endpoint_text":"- Time to other (non breast or ovarian cancer) malignancies, including those known to be associated with BRCA1 mutations","definition_or_measurement_approach":"Time-to-event (time from randomization to diagnosis of other malignancies)."}
- {"endpoint_text":"- Time to clinical fractures in pre- and postmenopausal women","definition_or_measurement_approach":"Time-to-event (time from randomization to occurrence of a clinical fracture)."}
- {"endpoint_text":"- Frequency of breast biopsies and frequency of benign breast lesions","definition_or_measurement_approach":"Frequency/rate measures (counts or rates of biopsies and benign breast lesion diagnoses during follow-up)."}
Recruitment
- Planned Sample Size
- 1768
- Recruitment Window Months
- 134
- Consent Approach
- Written informed consent is required: "Written informed consent before any study-specific procedure is performed". Consent is provided by the participant (adult women). ICF and subject information documents are present (L1_SIS and ICF_Main and translated/region-specific versions), including German and Spanish translations referenced in the application documents.
Geography
- Total Number Of Sites
- 16
- Total Number Of Participants
- 1150
Austria
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 20-08-2024
- Processing Time Days
- 29
- Number Of Sites
- 4
- Number Of Participants
- 400
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Allg. Gyn. u. gyn. Onkologie/Senologie
- Principal Investigator Name
- Christian Singer
- Principal Investigator Email
- christian.singer@meduniwien.ac.at
- Contact Person Name
- Christian Singer
- Contact Person Email
- christian.singer@meduniwien.ac.at
- Site Name
- Ordensklinikum Linz GmbH
- Department Name
- Chir. Abteilung
- Principal Investigator Name
- Ruth Helfgott
- Principal Investigator Email
- ruth.helfgott@ordensklinikum.at
- Contact Person Name
- Ruth Helfgott
- Contact Person Email
- ruth.helfgott@ordensklinikum.at
- Site Name
- Hanusch Krankenhaus Der Wiener Gebietskrankenkasse
- Department Name
- Zentrum f. Med. Genetik
- Principal Investigator Name
- Gökhan Uyanik
- Principal Investigator Email
- goekhan.uyanik@oegk.at
- Contact Person Name
- Gökhan Uyanik
- Contact Person Email
- goekhan.uyanik@oegk.at
- Site Name
- Medical University Of Graz
- Department Name
- Klin. Abt. f. Gynäkologie
- Principal Investigator Name
- Gunda Pristauz-Telsnigg
- Principal Investigator Email
- gunda.pristauz@klinikum-graz.at
- Contact Person Name
- Gunda Pristauz-Telsnigg
- Contact Person Email
- gunda.pristauz@klinikum-graz.at
Spain
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 14-08-2024
- Processing Time Days
- 23
- Number Of Sites
- 7
- Number Of Participants
- 250
Sites
- Site Name
- Complexo Hospitalario Universitario A Coruna
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- María Eva Pérez López
- Principal Investigator Email
- maria.eva.perez.lopez@sergas.es
- Contact Person Name
- María Eva Pérez López
- Contact Person Email
- maria.eva.perez.lopez@sergas.es
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Judith Balmana
- Principal Investigator Email
- jbalmana@vhio.net
- Contact Person Name
- Judith Balmana
- Contact Person Email
- jbalmana@vhio.net
- Site Name
- Hospital San Pedro De Alcantara
- Department Name
- Servicio de Oncología
- Principal Investigator Name
- Santiago González
- Principal Investigator Email
- sgonzalezs@seom.org
- Contact Person Name
- Santiago González
- Contact Person Email
- sgonzalezs@seom.org
- Site Name
- Institut Catala D'oncologia
- Department Name
- Genetic Counseling Unit
- Principal Investigator Name
- Iris Teruel
- Principal Investigator Email
- iteruel@iconcologia.net
- Contact Person Name
- Iris Teruel
- Contact Person Email
- iteruel@iconcologia.net
- Site Name
- Institut Catala D'oncologia
- Department Name
- Genetic Counseling Unit
- Principal Investigator Name
- Àlex Teulé
- Principal Investigator Email
- ateule@iconcologia.net
- Contact Person Name
- Àlex Teulé
- Contact Person Email
- ateule@iconcologia.net
- Site Name
- Hospital De La Santa Creu I Sant Pau
- Department Name
- Oncología Médica
- Principal Investigator Name
- Amaya Ramírez de Olano
- Principal Investigator Email
- ARamirezDe@santpau.cat
- Contact Person Name
- Amaya Ramírez de Olano
- Contact Person Email
- ARamirezDe@santpau.cat
- Site Name
- Institut Catala D'oncologia
- Department Name
- Servicio de Oncología Médica
- Principal Investigator Name
- Joan Brunet
- Principal Investigator Email
- jbrunet@iconcologia.net
- Contact Person Name
- Joan Brunet
- Contact Person Email
- jbrunet@iconcologia.net
Germany
- Earliest CTIS Part Ii Submission Date
- 22-07-2024
- Latest Decision Or Authorization Date
- 16-08-2024
- Processing Time Days
- 25
- Number Of Sites
- 5
- Number Of Participants
- 500
Sites
- Site Name
- Klinikum der Universitaet Muenchen AöR
- Department Name
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
- Principal Investigator Name
- Rachel Würstlein
- Principal Investigator Email
- rachel.wuerstlein@med.uni-muenchen.de
- Contact Person Name
- Rachel Würstlein
- Contact Person Email
- rachel.wuerstlein@med.uni-muenchen.de
- Site Name
- University Hospital Cologne AöR
- Department Name
- Center for Hereditary Breast and Ovarian Cancer
- Principal Investigator Name
- Kerstin Rhiem
- Principal Investigator Email
- kerstin.rhiem@uk-koeln.de
- Contact Person Name
- Kerstin Rhiem
- Contact Person Email
- kerstin.rhiem@uk-koeln.de
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Klinik f. Gynäkologie mit Brustzentrum. Zentrum Familiärer Brust- u. Eierstockkrebs
- Principal Investigator Name
- Jenny Katharina Wagner
- Principal Investigator Email
- jenny-katharina.wagner@charite.de
- Contact Person Name
- Jenny Katharina Wagner
- Contact Person Email
- jenny-katharina.wagner@charite.de
- Site Name
- Technische Universitaet Dresden
- Department Name
- Klinik und Poliklinik für Frauenheilkunde und Geburtshilfe
- Principal Investigator Name
- Cornelia Meisel
- Principal Investigator Email
- cornelia.meisel@ukdd.de
- Contact Person Name
- Cornelia Meisel
- Contact Person Email
- cornelia.meisel@ukdd.de
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Zentrum für familiaren Brust- und Eierstockkrebs
- Principal Investigator Name
- Alma Müller-Rausch
- Principal Investigator Email
- a.rausch@uke.de
- Contact Person Name
- Alma Müller-Rausch
- Contact Person Email
- a.rausch@uke.de
Sponsor
Primary sponsor
- Full Name
- Verein Zur Praevention Und Therapie Boesartiger Erkrankungen Austrian Breast And Colorectal Cancer Study Group
- Organisation Type
- Patient organisation/association
- Country Of Registered Address
- Austria
Co-sponsors
- Institut Catala D'oncologia
- ANZ Breast Cancer Trials Group Limited
- University Of Manchester
- Alliance Foundation Trials LLC
- Shaare Zedek Medical Center
Investigational products
- Investigational Product Name
- XGEVA 120 mg solution for injection
- Active Substance
- DENOSUMAB
- Modality
- Monoclonal antibody
- Routes Of Administration
- Subcutaneous
- Route
- Subcutaneous
- Authorisation Status
- Marketing authorisation (EU: EU/1/11/703/001)
- Starting Dose
- 120 mg
- Dose Levels
- 120 mg
- Maximum Dose
- 1200 mg (total)
- Investigational Product Name
- Identical to the Test product
- Modality
- Other
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