CLEAR-B: Cancer Landscape - Early Adjuvant Retrospective Registry - Breast Cancer (CLEAR-B)

May 12, 2023 updated by: Institut fuer Frauengesundheit

Cancer Landscape - Early Adjuvant Retrospective Registry - Breast Cancer (CLEAR-B)

This is a non-interventional retrospective cohort study of premenopausal patients with HR+/HER2- breast cancer who are treated in the adjuvant setting with either Tamoxifen, Tamoxifen + Ovarial Function Suppression or Aromatase inhibitor + Ovarial Function Suppression.

Study Overview

Status

Recruiting

Conditions

Detailed Description

The treatment landscape concerning the adjuvant endocrine therapy in premenopausal patients with early-stage hormone receptor positive (HRpos) breast cancer is quite heterogeneous and therapy recommendations can vary. Tamoxifen (TAM) is a common treatment option that does not require OFS, but research suggests that adding OFS to tamoxifen may improve outcomes. Aromatase inhibitors (AI) are another option, but they can only be used with OFS for premenopausal patients. Studies have shown that AI + OFS improves disease-free survival compared to TAM + OFS, but it may lead to additional side effects such as osteopenia and bone fractures.

The CLEAR-B study aims to provide a detailed description of the therapy landscape in this therapeutic setting, including recurrence rates and overall survival with AI compared to TAM, as well as a comparison of the chosen therapies within prognostic subgroups.

CLEAR-B is a retrospective cohort study, collecting data of premenopausal patients who were diagnosed with early-stage breast cancer between January 2016 and June 2019 in a certified breast cancer center. These patients had an intermediate or high risk of cancer recurrence, as defined by (neo)adjuvant chemotherapy, and/or pT≥2cm at the timepoint of definitive surgery and/or at least one positive lymph node at the time of definite surgery (pN+).

The primary objective is to compare the invasive disease-free survival (iDFS) of patients who were treated with AI + OFS vs. those who were treated with TAM ± OFS. Additionally, the study will compare distant disease-free survival (DDFS) and overall survival (OS) between the two groups and perform subgroup analyses according to risk stratification (stage II and III). This study will be conducted at around 75 certified breast cancer centers and will enroll up to 3000 patients.

Study Type

Observational

Enrollment (Anticipated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Germany
      • Erlangen, Germany, 91054
        • Recruiting
        • Department of Gynecology and Obstetrics, Erlangen University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Premenopausal patients with early-stage breast cancer who have been diagnosed from January 2016 to June 2019 with an intermediate or high recurrence risk in a certified breast cancer center (DKG/DGS).

Description

Inclusion Criteria:

  • Female patients with a first primary diagnosis of hormone receptor-positive, HER2- negative unilateral early breast cancer for whom an endocrine treatment is indicated
  • Patients must be at least 18 years of age but not older than 60

  • Premenopausal defined as all statements must be true

    • No oophorectomy before the diagnosis of breast cancer
    • Women with uterus: Regular, physiological menses at the timepoint of therapy decision for anti-endocrine treatment in the absence of contraceptives and hormonal treatment
    • Women without uterus and remaining ovaries: premenopausal hormone levels must be documented at the time of therapy decision for anti-endocrine treatment

  • Patients with an intermediate or high-risk early-stage breast cancer defined as: At least one of the following must be fulfilled

    • (Neo)adjuvant chemotherapy
    • pT≥2cm at the timepoint of definitive surgery
    • at least one positive lymph node at the time of definite surgery (pN+)
  • Patient must be previously registered in and must have been documented as part of the certification process for a certified breast cancer center according to the Deutsche Krebsgesellschaft/Deutsche Gesellschaft für Senologie
  • Breast Cancer must have been diagnosed between Jan 2016 and Jun 2019

Exclusion Criteria:

  • Patients with a low recurrence risk (see inclusion criteria for definition)
  • Locally advanced breast cancer or distant metastases at diagnosis
  • Male biological sex
  • Patients not treated in a certified breast cancer center
  • Treatment with CDK4/6Previous diagnosis of invasive breast cancer or in situ breast cancer
  • Concurrent invasive malignancy
  • Bilateral breast cancer at the timepoint of diagnosis
  • Previous diagnosis of invasive breast cancer or in situ breast cancer is not allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
AI+OFS
adjuvant treatment with aromatase inhibitor + OFS (ovarian function suppression)
TAM
Patients started the adjuvant treatment with Tamoxifen ± OFS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
iDFS
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years

The primary study aim is to show that aromatase inhibitor (AI) based treatments (AI arm) are not inferior to treatments based on tamoxifen (tamoxifen arm) in terms of invasive diseasefree survival (iDFS).

iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of iDFS
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years

In case non-inferiority is confirmed, the superiority of Cohort AI+OFS over Cohort TAM will be tested with regard to iDFS.

iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of DDFS
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
To analyze the non-inferiority of the Cohort AI+OFS compared with the Cohort TAM with regard to distant disease-free survival (DDFS). DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of OS
Time Frame: First start of adjuvant endocrine therapy until date of death up to 5 years

To analyze the non-inferiority of the Cohort AI+OFS compared with the Cohort TAM with regard to overall survival (OS). In case non-inferiority is confirmed, the superiority of Cohort AI+OFS over Cohort TAM will be tested with regard to OS.

OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
First start of adjuvant endocrine therapy until date of death up to 5 years
Comparison of iDFS in Cohort TAM
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
To compare patients within the Cohort TAM who were treated with OFS and those who were not treated with OFS. iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of DDFS in Cohort TAM
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
To compare patients within the Cohort TAM who were treated with OFS and those who were not treated with OFS. DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of OS in Cohort TAM
Time Frame: First start of adjuvant endocrine therapy until date of death up to 5 years
To compare patients within the Cohort TAM who were treated with OFS and those who were not treated with OFS. OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
First start of adjuvant endocrine therapy until date of death up to 5 years
Comparison of iDFS (TAM+OFS and AI+OFS)
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years

To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were treated with OFS with regard to iDFS.

iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of DDFS (TAM+OFS and AI+OFS)
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were treated with OFS with regard to DDFS. DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of OS (TAM+OFS and AI+OFS)
Time Frame: First start of adjuvant endocrine therapy until date of death up to 5 years

To compare patients of Cohort AI+OFS with patients in Cohort TAM who were treated with OFS.

OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
First start of adjuvant endocrine therapy until date of death up to 5 years
Comparison of iDFS (TAM-OFS and AI+OFS)
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years

To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were not treated with OFS with regard to iDFS.

iDFS will be assessed as time to event. Events for iDFS include: Invasive Ipsilateral Breast Tumor Recurrence (IBTR), Local/Regional Invasive Recurrence, Distant Recurrence, Death from BC, Death from Non-BC Cause, Death From unknown cause, Invasive Contralateral BC, Second Primary Invasive Cancer (non-breast)
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of DDFS (TAM-OFS and AI+OFS)
Time Frame: First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years

To compare patients of Cohort AI+OFS with patients in Cohort TAM, who were not treated with OFS with regard to DDFS.

DDFS will be assessed as time to event. Events for DDFS include distant recurrence, death from breast cancer, death from non-breast cancer cause, death from unknown cause.
First start of adjuvant endocrine therapy until date of the above mentioned events up to 5 years
Comparison of OS (TAM-OFS and AI+OFS)
Time Frame: First start of adjuvant endocrine therapy until date of death up to 5 years

To compare patients of Cohort AI+OFS with patients in Cohort TAM who were not treated with OFS.

OS is defined as time from first start of adjuvant endocrine therapy until date of death due to any cause.
First start of adjuvant endocrine therapy until date of death up to 5 years
Influence of disease stage
Time Frame: Baseline until onset of disease progression or death up to 5 years
To conduct multivariate analyses to estimate the influence of disease stage on prognosis.
Baseline until onset of disease progression or death up to 5 years
Risk Factors
Time Frame: Baseline until onset of disease progression or death up to 5 years
To conduct subgroup analyses for the survival outcomes (iDFS, DDFS, OS) according to risk stratification (stage II and stage III)
Baseline until onset of disease progression or death up to 5 years
NATALEE Comparison
Time Frame: Baseline until onset of disease progression or death up to 5 years
To compare patients who are matching the inclusion and exclusion criteria of the pivotal study NATALEE and who were treated in Cohort AI+OFS with patients matching the NATALEE population and who were treated in Cohort TAM.
Baseline until onset of disease progression or death up to 5 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Therapy frequencies
Time Frame: Baseline
To assess the frequency of the different therapies according to risk groups
Baseline
Adherence
Time Frame: End of Treatment/ Treatment termination up to 5 years
Number of patients with specified reason for therapy termination (recurrence, side effects, patients' wishes etc.)
End of Treatment/ Treatment termination up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut fuer Frauengesundheit

Collaborators

Novartis Pharmaceuticals
AGO Breast Study Group e.V.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2023

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

December 1, 2023

Study Registration Dates

First Submitted

April 14, 2023

First Submitted That Met QC Criteria

May 12, 2023

First Posted (Actual)

May 23, 2023

Study Record Updates

Last Update Posted (Actual)

May 23, 2023

Last Update Submitted That Met QC Criteria

May 12, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IFG-02-2022
  • AGOB-059 (Other Identifier: AGO breast study group)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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