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

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ClinicalTrials.gov Identifier: NCT05452213
Recruitment Status : Recruiting
First Posted : July 11, 2022
Last Update Posted : April 18, 2023
Sponsor:
Collaborators:
AGO Breast Study Group e.V.
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Institut fuer Frauengesundheit

Tracking Information
First Submitted Date  ICMJE June 28, 2022
First Posted Date  ICMJE July 11, 2022
Last Update Posted Date April 18, 2023
Actual Study Start Date  ICMJE October 12, 2022
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 8, 2022)
  • 12-month PFS rate [ Time Frame: 12 months ]
    The rate for progression-free survival at month 12 will be calculated.
  • 12-month OS rate [ Time Frame: 12 months ]
    The rate for overall survival at month 12 will be calculated.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 8, 2022)
  • 24-month PFS rate [ Time Frame: 24 months ]
    The rate for progression-free survival at month 24 will be calculated.
  • 24-month OS rate [ Time Frame: 24 months ]
    The rate for overall survival at month 24 will be calculated.
  • 36-month PFS rate [ Time Frame: 36 months ]
    The rate for progression-free survival at month 36 will be calculated.
  • 36-month OS rate [ Time Frame: 36 months ]
    The rate for overall survival at month 36 will be calculated.
  • Median progression-free survival [ Time Frame: 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. ]
    Median progression-free survival will be estimated if achieved at the end of study
  • Median overall survival [ Time Frame: From date of enrollment until date of death from any cause or regular end of study (up to 24 months) whichever is first. ]
    Median overall survival will be estimated if achieved at the end of study
  • Health related quality of life (FACT-G) [ Time Frame: Collected before start of trial treatment, at 3 months and every 6 months afterwards until end of study up to 24 months ]
    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.
  • Health related quality of life (FACT-B) [ Time Frame: Collected before start of trial treatment, at 3 months and every 6 months afterwards until end of study up to 24 months ]
    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.
  • Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: All adverse events will be recorded from signing informed consent through 30 days following cessation of treatment or until the last study visit ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 8, 2022)
  • Correlation of genome wide genetic biomarkers with progression-free survival [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide genetic biomarkers with overall survival [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide genetic biomarkers with quality of life [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide genetic biomarkers with ribociclib side effects [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide gene expression biomarkers with progression-free survival [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide gene expression biomarkers with overall survival [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide gene expression biomarkers with quality of life [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide gene expression biomarkers with ribociclib side effects [ Time Frame: 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. ]
    Genome wide genetic biomarkers will be assessed by whole genome sequencing and/ or panel sequencing from blood samples.
  • Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with progression-free survival [ Time Frame: Measured from biomaterial collected at baseline and at the time of tumor progression ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with overall survival [ Time Frame: Measured from biomaterial collected at baseline and at the time of tumor progression ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with quality of life [ Time Frame: Measured from biomaterial collected at baseline and at the time of tumor progression ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from formalin-fixed paraffin embedded tumor material with ribociclib side effects [ Time Frame: Measured from biomaterial collected at baseline and at the time of tumor progression ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with progression-free survival [ Time Frame: 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. ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with overall survival [ Time Frame: 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. ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with quality of life [ Time Frame: 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. ]
    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.
  • Correlation of genome wide tumor mutational patterns assessed from ctDNA biomarkers with ribociclib side effects [ Time Frame: 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. ]
    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.
  • Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with progression-free survival [ Time Frame: 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. ]
    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.
  • Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with overall survival [ Time Frame: 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. ]
    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.
  • Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with quality of life [ Time Frame: 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. ]
    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.
  • Correlation of changes in the genome wide tumor mutational patterns assessed from ctDNA biomarkers with ribociclib side effects [ Time Frame: 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. ]
    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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
Official Title  ICMJE CAPTOR-BC: Comprehensive Analysis of Spatial, Temporal and Molecular Patterns of Ribociclib Efficacy and Resistance in Advanced Breast Cancer Patients
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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
One-arm, open-label
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasm Female
  • Breast Cancer Female
  • HER2-negative Breast Cancer
  • Hormone Receptor-positive Breast Cancer
  • Advanced Breast Cancer
Intervention  ICMJE 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.

Study Arms  ICMJE Experimental: Ribociclib
Intervention: Drug: Ribociclib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 8, 2022)
1000
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2026
Estimated Primary Completion Date October 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: CAPTOR Study Manager 09131 9278638 captor@ifg-erlangen.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05452213
Other Study ID Numbers  ICMJE IFG-01-2022
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Institut fuer Frauengesundheit
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Institut fuer Frauengesundheit
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • AGO Breast Study Group e.V.
  • Novartis Pharmaceuticals
Investigators  ICMJE
Study Chair: Peter A. Fasching, MD, Prof. Department of Gynecology and Obstetrics, Erlangen University Hospital
Study Chair: Tanja Fehm, MD, Prof. Department of Gynecology/Obstetrics |University Hospital Düsseldorf, Germany
Study Chair: Andreas Schneeweiss, MD, Prof. National Center for Tumor Diseases (NCT) | Heidelberg University Hospital and German Cancer Research Center
PRS Account Institut fuer Frauengesundheit
Verification Date April 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP