Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients

Breast Cancer Clinical Trial

— CAPTOR-BC  

Official title:

CAPTOR-BC: Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05452213
• Other study ID #: IFG-01-2022
• Status: Recruiting
• Phase: Phase 4
• Start date: October 12, 2022
• Est. completion date: October 2026

Study information

• Verified date: April 2023
• Source: Institut fuer Frauengesundheit
• Contact: CAPTOR Study Manager
• Phone: 09131 9278638
• Email: captor[@]ifg-erlangen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: October 2026
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Breast Cancer
• Breast Cancer Female
• Breast Neoplasm Female
• Breast Neoplasms
• HER2-negative Breast Cancer
• Hormone Receptor-positive Breast Cancer
• Neoplasms

Intervention

Drug:
• Ribociclib
All patients will receive ribociclib in combination with standard endocrine therapy according to the current SmPC and local in-house standard. Ribociclib will be administered once daily for 21 consecutive days followed by 7 days off treatment (28-day cycle). The daily dose is 600 mg/day. Ribociclib and standard of care endocrine treatment will be prescribed and administered according to investigator's discretion.

Locations

Country	Name	City	State
Germany	Klinikum St Marien Amberg	Amberg
Germany	Onkologie Aschaffenburg, Hämato-Onkologische Schwerpunktpraxis am Klinikum Aschaffenburg	Aschaffenburg
Germany	Klinik für Hämatologie und Onkologie, Uniklinik Augsburg	Augsburg
Germany	University Hospital Augsburg	Augsburg
Germany	Frauenklinik des Klinikums Bamberg	Bamberg
Germany	HELIOS Klinikum Berlin-Buch	Berlin
Germany	MediOnko GbR	Berlin
Germany	Zentrum für ambulante Hämatologie und Onkologie (ZAHO) an der Robert-Janker-Klinik	Bonn
Germany	Department for Gynecology and Obstetrics, Marienhospital Bottrop gGmbH	Bottrop	North Rhine-Westphalia
Germany	Klinik für Gynäkologie, Gynäkoonkologie und Senologie Klinikum Bremen-Mitte	Bremen
Germany	Klinikum Chemnitz gGmbH, Klinik für Frauenheilkunde und Geburtshilfe	Chemnitz
Germany	Kliniken Der Stadt Köln gGmbH	Cologne
Germany	Carl-Thiem-Klinikum Cottbus	Cottbus
Germany	Staedtisches Klinikum Dessau, Gynecology and Obstetrics	Dessau
Germany	Universitäts-Frauenklinik Carl Gustav Carus Universität Dresden	Dresden
Germany	Universitaetsklinikum Duesseldorf AöR	Duesseldorf
Germany	Department of Gynecology and Obstetrics, Erlangen University Hospital	Erlangen	Bavaria
Germany	Universitaetsklinikum Essen AöR, Gynecology and Obstetrics	Essen
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Agaplesion Frankfurter Diakonie Kliniken gGmbH, Gynecology and Obstetrics	Frankfurt Am Main
Germany	Universitäts-Frauenklinik Frankfurt	Frankfurt am Main
Germany	Universitäts-Frauenklinik Freiburg	Freiburg
Germany	Medizinisches Versorgungszentrum Onkologie Georgsmarienhütte und Bramsche	Georgsmarienhütte
Germany	Mammazentrum Hamburg am Krankenhaus Jerusalem	Hamburg
Germany	Universitäts-Frauenklinik Hamburg-Eppendorf	Hamburg
Germany	Nationales Centrum für Tumorerkrankungen, Universitätsklinikum Heidelberg Abteilung für Gynäkologie und Geburtshilfe	Heidelberg
Germany	Frauenklinik, SLK-Kliniken Heilbronn GmbH	Heilbronn
Germany	Staedtisches Klinikum Karlsruhe gGmbH, Gynecology and Obstetrics	Karlsruhe
Germany	University Medical Centre Schleswig-Holstein, Gynecology and Obstetrics	Kiel
Germany	ZAGO-Zentrum für ambulante gynäkologische Onkologie	Krefeld
Germany	Klinikum Kulmbach	Kulmbach
Germany	VK&K Studienzentrum Landshut am Lakumed Klinikum Landshut-Achdorf	Landshut
Germany	Praxis Dr. Müller MVM GmbH, Studienzentrum UnterEms	Leer
Germany	Universitäts-Frauenklinik Leipzig	Leipzig
Germany	Department of Gynecology and Obstetrics, University Medicine Mainz	Mainz	Hesse
Germany	Ev. Krankenhaus Bethesda Mönchengladbach	Mönchengladbach
Germany	Hämatologie Onkologie Gemeinschaftspraxis Pasing	Munich
Germany	MVZ Nordhausen gGmbH	Nordhausen
Germany	Klinikum Nürnberg	Nuremberg
Germany	Frauenklinik, Medius Klinik Nürtingen	Nürtingen
Germany	Gemeinschaftspraxis für Hämatologie und Onkologie GbR	Ravensburg
Germany	Frauenklinik, Diakoniekrankenhaus Rotenburg	Rotenburg
Germany	Leopoldina Krankenhaus der Stadt Schweinfurt gGmbH	Schweinfurt
Germany	Schwerpunktpraxis für Hämatologie, Onkologie und Magen-Darm Diagnostik	Singen
Germany	Onkologische Schwerpunktpraxis Speyer	Speyer
Germany	Klinikum Stuttgart	Stuttgart
Germany	Onkologie Rheinsieg, Praxisnetzwerk Hämatologie und internistische Onkologie	Troisdorf
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Germany	Universitäts-Frauenklinik Ulm	Ulm
Germany	MVZ Nordoberpfalz	Weiden
Germany	Medizinische Studiengesellschaft Nord-West GmbH	Westerstede
Germany	Rems-Murr Kliniken Winnenden	Winnenden

Sponsors (3)

Lead Sponsor	Collaborator
Institut fuer Frauengesundheit	AGO Breast Study Group e.V., Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of genome wide genetic biomarkers with progression-free survival	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide genetic biomarkers with overall survival	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide genetic biomarkers with quality of life	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide genetic biomarkers with ribociclib side effects	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide gene expression biomarkers with progression-free survival	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide gene expression biomarkers with overall survival	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide gene expression biomarkers with quality of life	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide gene expression biomarkers with ribociclib side effects	Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.	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.
Other	Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with progression-free survival	Tumor DNA will be either isolated from FFPE tissue (primary tumor or metastasis) or from Plasma samples (STRECK cfDNA Tube). DNA will be analyzed by whole genome sequencing and/or panel sequencing.	Measured from biomaterial collected at baseline and at the time of tumor progression
Other	Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with overall survival	Tumor DNA will be either isolated from FFPE tissue (primary tumor or metastasis) or from Plasma samples (STRECK cfDNA Tube). DNA will be analyzed by whole genome sequencing and/or panel sequencing.	Measured from biomaterial collected at baseline and at the time of tumor progression
Other	Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with quality of life	Tumor DNA will be either isolated from FFPE tissue (primary tumor or metastasis) or from Plasma samples (STRECK cfDNA Tube). DNA will be analyzed by whole genome sequencing and/or panel sequencing.	Measured from biomaterial collected at baseline and at the time of tumor progression
Other	Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with ribociclib side effects	Tumor DNA will be either isolated from FFPE tissue (primary tumor or metastasis) or from Plasma samples (STRECK cfDNA Tube). DNA will be analyzed by whole genome sequencing and/or panel sequencing.	Measured from biomaterial collected at baseline and at the time of tumor progression
Other	Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with progression-free survival	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with overall survival	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with quality of life	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with ribociclib side effects	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with progression-free survival	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with overall survival	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with quality of life	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Other	Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with ribociclib side effects	Germline DNA will be isolated from one EDTA blood samples obtained within the study. DNA will be analyzed by whole genome sequencing and/or panel sequencing.	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.
Primary	12-month PFS rate	The rate for progression-free survival at month 12 will be calculated.	12 months
Primary	12-month OS rate	The rate for overall survival at month 12 will be calculated.	12 months
Secondary	24-month PFS rate	The rate for progression-free survival at month 24 will be calculated.	24 months
Secondary	24-month OS rate	The rate for overall survival at month 24 will be calculated.	24 months
Secondary	36-month PFS rate	The rate for progression-free survival at month 36 will be calculated.	36 months
Secondary	36-month OS rate	The rate for overall survival at month 36 will be calculated.	36 months
Secondary	Median progression-free survival	Median progression-free survival will be estimated if achieved at the end of study	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.
Secondary	Median overall survival	Median overall survival will be estimated if achieved at the end of study	From date of enrollment until date of death from any cause or regular end of study (up to 24 months) whichever is first.
Secondary	Health related quality of life (FACT-G)	Health related quality of life as assessed by FACT-G questionnaire (Functional Assessment of Cancer Therapy - General) Min 0, Max 108, The higher the score, the better the QoL.	Collected before start of trial treatment, at 3 months and every 6 months afterwards until end of study up to 24 months
Secondary	Health related quality of life (FACT-B)	Health related quality of life as assessed by FACT-B questionnaire (Functional Assessment of Cancer Therapy - Breast Cancer) Min 0, Max 148, The higher the score, the better the QoL.	Collected before start of trial treatment, at 3 months and every 6 months afterwards until end of study up to 24 months
Secondary	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	The safety endpoints for the study will include rate of adverse events (AE), serious adverse events (SAEs) and fatal SAEs, causality and outcome of AE/SAEs, rate of treatment discontinuations and reasons, Changes in vital signs, laboratory values etc. Grading of AE/SAEs will be based on NCI CTCAE v5.0.	All adverse events will be recorded from signing informed consent through 30 days following cessation of treatment or until the last study visit