Clinical trial NCT05452213: Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
Official title: CAPTOR-BC: Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Breast Cancer
Breast Neoplasms
Breast Neoplasm Female
Breast Cancer Female
HER2-negative Breast Cancer
Hormone Receptor-positive Breast Cancer
Advanced Breast Cancer
Lead sponsor: Institut fuer Frauengesundheit
Sponsor class: OTHER
Collaborators: name: AGO Breast Study Group e.V.
name: Novartis Pharmaceuticals
First posted: 2022-07-11
Enrollment: 1000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: One-arm, open-label
Primary purpose: TREATMENT

Brief summary: This is a single-arm, open-label phase IV study of patients with advanced HR+/HER2- breast cancer who are treated first line with ribociclib and standard of care endocrine treatment according to SmPC.

Detailed description: This is a prospective, multicenter, phase IV, one-arm, open-label clinical trial investigating patients treated with ribociclib and standard of care endocrine therapy for hormone receptor positive (HR+) / human epidermal growth factor receptor negative (HER2-) advanced breast cancer in the first therapy line. Patients eligible for this trial will receive on-label ribociclib according to Summary of Product Characteristics (SmPC) and as well as the specified inclusion/exclusion criteria.

The survival rates for progression-free survival (PFS) and overall survival (OS) at month 12 are the co-primary objectives. Quality of life and toxicity are secondary objectives. Additionally, there is a comprehensive biomarker discovery and validation program included into the study.

A total of 1000 patients are planned to be enrolled into this trial in 75 trial sites in Germany.

Biomarkers will be evaluated before, during and after treatment or at progression. A comprehensive biospecimens sampling will be done to enable translational research projects and evaluation of potential biomarkers within circulation tumor desoxyribonucleic acid (ctDNA), circulating tumor ribonucleic acid (ctRNA), formaldehyde-fixed paraffin-embedded tissue (FFPE) tissue, Serum, Plasma and circulating immune cells

Eligibility criteria: Inclusion Criteria:

1. Indication for treatment with ribociclib in combination with endocrine therapy in the locally advanced or 1st line metastatic therapy setting according to SmPC. (Previous treatment with cycline dependent kinase 4/6 (CDK4/6) inhibitors is allowed in the adjuvant setting)
2. Written informed consent prior to beginning of trial specific procedures
3. Subject must be female and aged ≥ 18 years on the day of signing informed consent
4. Locally advanced or metastatic breast cancer not amenable to curative treatment
5. Patient has HER2-negative breast cancer confirmed by local laboratory defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory
6. Histologically confirmed estrogen receptor (ER) positive and/ or progesterone receptor (PgR) positive breast cancer determined by core biopsy according to local in-house standard.
7. corrected QT (QTcF) interval \< 450 ms
8. Adequate organ function amenable for treatment with ribociclib as assessed by local laboratory
9. Women of childbearing potential must have a negative urine or serum pregnancy test within 72 h prior to study entry and be willing to use highly effective method of contraception for course of the trial through 21 days after the last dose of trial treatment.
10. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. Concurrent participation in a study with an investigational agent/device or within 14 days of study entry or 5 half-lives of the respective investigational agent/device, whichever is longer
2. Patients who are not treated for advanced HR+, HER2- breast cancer in the first line therapy setting.
3. Patient not eligible for treatment with ribociclib according to SmPC or investigator's discretion
4. Patients who are pregnant or lactating.
5. Patients with existing or patients who are at significant risk of developing corrected QT interval (QTc) prolongation. This includes

   * patients with long QT syndrome
   * uncontrolled or significant cardiac disease, including recent myocardial infarction, congestive heart failure, unstable angina and bradyarrhythmia
   * electrolyte abnormalities
6. Patients with known hypersensitivity to the active substance of ribociclib, soya, peanut or any other of the excipients of ribociclib.
7. Patients with active systemic infections (for example, bacterial infection requiring intravenous antibiotics at time of initiating study treatment, fungal infection, or detectable viral infection requiring systemic therapy) or viral load (such as known human immunodeficiency virus positivity or with known active hepatitis B or C, for example, hepatitis B surface antigen positive).
8. Patients with serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (such as severe renal impairment, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea).
9. Patient who do not agree to collection of biospecimens samples (blood, stool, tissue)

Primary outcomes:
measure: 12-month PFS rate
timeFrame: 12 months
measure: 12-month OS rate
timeFrame: 12 months
Secondary outcomes:
measure: 24-month PFS rate
timeFrame: 24 months
measure: 24-month OS rate
timeFrame: 24 months
measure: 36-month PFS rate
timeFrame: 36 months
measure: 36-month OS rate
timeFrame: 36 months
measure: Median progression-free survival
timeFrame: From date of enrollment until first documented progression or date of death from any cause or regular end of study (up to 24 months) whichever is first.
measure: Median overall survival
timeFrame: From date of enrollment until date of death from any cause or regular end of study (up to 24 months) whichever is first.
measure: Health related quality of life (FACT-G)
timeFrame: Collected before start of trial treatment, at 3 months and every 6 months afterwards until end of study up to 24 months
measure: Health related quality of life (FACT-B)
timeFrame: Collected before start of trial treatment, at 3 months and every 6 months afterwards until end of study up to 24 months
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
timeFrame: All adverse events will be recorded from signing informed consent through 30 days following cessation of treatment or until the last study visit
Other outcomes:
measure: Correlation of genome wide genetic biomarkers with progression-free survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide genetic biomarkers with overall survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide genetic biomarkers with quality of life
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide genetic biomarkers with ribociclib side effects
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide gene expression biomarkers with progression-free survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide gene expression biomarkers with overall survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide gene expression biomarkers with quality of life
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide gene expression biomarkers with ribociclib side effects
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with progression-free survival
timeFrame: Measured from biomaterial collected at baseline and at the time of tumor progression
measure: Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with overall survival
timeFrame: Measured from biomaterial collected at baseline and at the time of tumor progression
measure: Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with quality of life
timeFrame: Measured from biomaterial collected at baseline and at the time of tumor progression
measure: Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with ribociclib side effects
timeFrame: Measured from biomaterial collected at baseline and at the time of tumor progression
measure: Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with progression-free survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with overall survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with quality of life
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with ribociclib side effects
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with progression-free survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with overall survival
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with quality of life
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
measure: Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with ribociclib side effects
timeFrame: Measured from biomaterial collected at baseline, 2 weeks, 3 months, 6 months, 12 months, 18 months or at the end of treatment in case treatment is stopped irregularly.
Locations:
city: Erlangen
country: Germany
facility: Department of Gynecology and Obstetrics, Erlangen University Hospital
state: Bavaria
city: Mainz
country: Germany
facility: Department of Gynecology and Obstetrics, University Medicine Mainz
state: Hesse
city: Bottrop
country: Germany
facility: Department for Gynecology and Obstetrics, Marienhospital Bottrop gGmbH
state: North Rhine-Westphalia
city: Amberg
country: Germany
facility: Klinikum St Marien Amberg
city: Aschaffenburg
country: Germany
facility: Onkologie Aschaffenburg, Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg
city: Augsburg
country: Germany
facility: Klinik für Hämatologie und Onkologie, Uniklinik Augsburg
city: Augsburg
country: Germany
facility: University Hospital Augsburg
city: Bamberg
country: Germany
facility: Frauenklinik des Klinikums Bamberg
city: Berlin
country: Germany
facility: MediOnko GbR
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Bonn
country: Germany
facility: Zentrum für ambulante Hämatologie und Onkologie (ZAHO) an der Robert-Janker-Klinik
city: Bremen
country: Germany
facility: Klinik für Gynäkologie, Gynäkoonkologie und Senologie Klinikum Bremen-Mitte
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH, Klinik für Frauenheilkunde und Geburtshilfe
city: Cologne
country: Germany
facility: Kliniken Der Stadt Köln gGmbH
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus
city: Dessau
country: Germany
facility: Staedtisches Klinikum Dessau, Gynecology and Obstetrics
city: Dresden
country: Germany
facility: Universitäts-Frauenklinik Carl Gustav Carus Universität Dresden
city: Duesseldorf
country: Germany
facility: Universitaetsklinikum Duesseldorf AöR
city: Essen
country: Germany
facility: Universitaetsklinikum Essen AöR, Gynecology and Obstetrics
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Frankfurt Am Main
country: Germany
facility: Agaplesion Frankfurter Diakonie Kliniken gGmbH, Gynecology and Obstetrics
city: Frankfurt am Main
country: Germany
facility: Universitäts-Frauenklinik Frankfurt
city: Freiburg
country: Germany
facility: Universitäts-Frauenklinik Freiburg
city: Georgsmarienhütte
country: Germany
facility: Medizinisches Versorgungszentrum Onkologie Georgsmarienhütte und Bramsche
city: Hamburg
country: Germany
facility: Universitäts-Frauenklinik Hamburg-Eppendorf
city: Hamburg
country: Germany
facility: Mammazentrum Hamburg am Krankenhaus Jerusalem
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg Abteilung für Gynäkologie und Geburtshilfe
city: Heilbronn
country: Germany
facility: Frauenklinik, SLK-Kliniken Heilbronn GmbH
city: Karlsruhe
country: Germany
facility: Staedtisches Klinikum Karlsruhe gGmbH, Gynecology and Obstetrics
city: Kiel
country: Germany
facility: University Medical Centre Schleswig-Holstein, Gynecology and Obstetrics
city: Krefeld
country: Germany
facility: ZAGO-Zentrum für ambulante gynäkologische Onkologie
city: Kulmbach
country: Germany
facility: Klinikum Kulmbach
city: Landshut
country: Germany
facility: VK&K Studienzentrum Landshut am Lakumed Klinikum Landshut-Achdorf
city: Leer
country: Germany
facility: Praxis Dr. Müller MVM GmbH, Studienzentrum UnterEms
city: Leipzig
country: Germany
facility: Universitäts-Frauenklinik Leipzig
city: Munich
country: Germany
facility: Hämatologie Onkologie Gemeinschaftspraxis Pasing
city: Mönchengladbach
country: Germany
facility: Ev. Krankenhaus Bethesda Mönchengladbach
city: Nordhausen
country: Germany
facility: MVZ Nordhausen gGmbH
city: Nuremberg
country: Germany
facility: Klinikum Nürnberg
city: Nürtingen
country: Germany
facility: Frauenklinik, Medius Klinik Nürtingen
city: Ravensburg
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie GbR
city: Rotenburg
country: Germany
facility: Frauenklinik, Diakoniekrankenhaus Rotenburg
city: Schweinfurt
country: Germany
facility: Leopoldina Krankenhaus der Stadt Schweinfurt gGmbH
city: Singen
country: Germany
facility: Schwerpunktpraxis für Hämatologie, Onkologie und Magen-Darm Diagnostik
city: Speyer
country: Germany
facility: Onkologische Schwerpunktpraxis Speyer
city: Stuttgart
country: Germany
facility: Klinikum Stuttgart
city: Troisdorf
country: Germany
facility: Onkologie Rheinsieg, Praxisnetzwerk Hämatologie und internistische Onkologie
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Ulm
country: Germany
facility: Universitäts-Frauenklinik Ulm
city: Weiden
country: Germany
facility: MVZ Nordoberpfalz
city: Westerstede
country: Germany
facility: Medizinische Studiengesellschaft Nord-West GmbH
city: Winnenden
country: Germany
facility: Rems-Murr Kliniken Winnenden
Study officials:
affiliation: Department of Gynecology and Obstetrics, Erlangen University Hospital
name: Peter A. Fasching, MD, Prof.
role: STUDY_CHAIR
affiliation: Department of Gynecology/Obstetrics |University Hospital Düsseldorf, Germany
name: Tanja Fehm, MD, Prof.
role: STUDY_CHAIR
affiliation: National Center for Tumor Diseases (NCT) | Heidelberg University Hospital and German Cancer Research Center
name: Andreas Schneeweiss, MD, Prof.
role: STUDY_CHAIR
References: