Assessment of Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in ER-positive, Her2-negative Early Breast Cancer (OPTIGEN)

August 25, 2017 updated by: UNICANCER

Prospective Multicenter Randomized Study Assessing Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in Patients With ER-positive, Her2-negative Early Breast Cancer With Uncertainty on the Indication of Chemotherapy Using Standard Assessments.

The need/benefit of adjuvant chemotherapy could be negligible for a certain category of patient with newly diagnosed unilateral non metastatic breast cancer. Physicians are sometimes divided between the administration of adjuvant treatment and no administration when the risk of distant relapse at 10 years is around 10% with uncertainty and a theoretical benefit of chemotherapy is less than 5% at 10 years according to guidelines in use in the center.

Several genomic tests have been developed this last decade. These tests use a sample of breast cancer tissue to analyze the activity of a group of genes. Knowing whether certain genes are present or absent, overly active or not active enough, can help physicians predict the risk of recurrence.

In addition to standard pathological characteristics, a genomic test could be helpful in making treatment decisions, such as whether or not chemotherapy should be part of the treatment plan. First generation prognostic tests are currently widely used worldwide to guide decision making regarding adjuvant chemotherapy (OncotypeDX™ Mammaprint®). Prognostic tests have reached a level of evidence 1A, with the results of the prospective randomized trial "Mindact". In the "Mindact" trial, among women with early-stage breast cancer who were at high clinical risk and low genomic risk for recurrence, the receipt of no chemotherapy on the basis of the 70-gene signature led to a 5-year rate of survival without distant metastasis that was 1.5 percentage points lower than the rate with chemotherapy. Given these findings, approximately 46% of women with breast cancer who are at high clinical risk might not require chemotherapy. The health-economic value of such signatures in the general population of patients with localized breast cancer appears very low at current costs.

Meanwhile, next generation prognostic signatures have been developed that have integrated clinical parameters and suggest high added value beyond all standard and traditional characteristics including tumor burden, grade, Estrogen Receptor (ER) and Progesterone Receptor (PR), Her2, age and also standard assessment of proliferation.

In this study, the clinical utility of genomic tests (Endopredict®, Prosigna®, OncotypeDX®, Mammaprint® assay) defined as impact on chemotherapy decision in the adjuvant setting in patients with ER-positive, Her2-negative early breast cancer with uncertainty on the indication of chemotherapy using standard assessments will be compared.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Woman, Age ≥ 18 years;
  2. Performance status 0 or 1 (according to World Health Organization criteria);
  3. Patient with newly diagnosed, unilateral, localized, histologically confirmed, invasive breast cancer; Note: Multicentric/multifocal tumors are allowed provided a maximum of 3 lesions are present, and all are ER > 10% or Allred ≥ 4, Her2-negative (genomic test will be performed on the lesion considered the most pertinent by the multidisciplinary team)
  4. Fully operated breast cancer including complete resection of breast tumor and adequate axillary surgery;
  5. Available surgical material (formalin-fixed, paraffin-embedded) for genomic test evaluation;
  6. ER-positive by immuno-histochemical (>10% cells stained or Allred Score≥4);
  7. HER2-negative by IHC (score 0 or 1+) and/or fluorescence in situ hybridization/silver in situ hybridization/chemiluminescent in situ hybridization ;

  8. Uncertainty regarding the toxicity/benefit of adjuvant chemotherapy, outlined in the following situations:

    • Grade 1: pT3 or 1-3 node positive
    • Grade 2: pT1 pN0 but high proliferation (Ki67 >20%) or lympho-vascular emboli, or 1-3 node positive
    • Grade 2 : pT2 pN0
    • Grade 3: pT1 pN0
  9. Adequate renal, hepatic, cardiac and hematopoietic functions for a chemotherapy administration;
  10. Willingness and ability to comply with scheduled visits as well as with test results and chemotherapy decision according to the latest;
  11. Signed informed consent and Health insurance coverage.

Exclusion Criteria:

  1. Non operable, bilateral, locally advanced, T4 or metastatic breast cancer;
  2. HER2 Overexpression, as assessed by 3+ IHC or FISH/SISH/CISH amplification;
  3. Diagnosis of any previous malignancy within the last 5 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma, or in situ cervical carcinoma;
  4. Any previous systemic or locoregional treatment for the present breast cancer;
  5. Documented inherited predisposition with BRCA1/2 or TP53 mutation;
  6. Previous hormone replacement therapy (HRT) stopped less than 2 weeks before surgery;
  7. Previous treatment for the present breast cancer;
  8. Person unable to give informed consent.

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

  • Primary Purpose: DIAGNOSTIC
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Endopredict®
genomic test Endopredict® realized on surgery tumour samples
Diagnostic test: Genomic test
genomic test realized on surgery block or formalin-fixed paraffin-embedded slides
ACTIVE_COMPARATOR: Prosigna®
genomic test Prosigna® realized on surgery tumour samples
Diagnostic test: Genomic test
genomic test realized on surgery block or formalin-fixed paraffin-embedded slides
ACTIVE_COMPARATOR: OncotypeDX®
genomic test OncotypeDX® realized on surgery tumour samples
Diagnostic test: Genomic test
genomic test realized on surgery block or formalin-fixed paraffin-embedded slides
ACTIVE_COMPARATOR: Mammaprint® assay
genomic test Mammaprint® assay realized on surgery tumour samples
Diagnostic test: Genomic test
genomic test realized on surgery block or formalin-fixed paraffin-embedded slides

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Comparison of genomic tests clinical utility
Time Frame: At the end of the inclusion period: 12 months
Pairwise comparisons between genomic tests in terms of percentage of changes between initial adjuvant chemotherapy decision and final receipt of chemotherapy (yes/no)
At the end of the inclusion period: 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Distant disease-free survival in patients who do not receive chemotherapy
Time Frame: 5 years
5-year distant disease-free survival among the pooled cohort of patients who did not receive chemotherapy
5 years
Distant disease-free survival in patients who do not receive chemotherapy based on genomic test result.
Time Frame: 5 years
5-year distant disease-free survival in patients who did not receive chemotherapy based on genomic test result
5 years
Reason for discordant final decision when they occur
Time Frame: 12 months
Number of decision changes according to the test results. Physicians' and patients' reasons for "non-compliance" with the test's results will be recorded (a threshold at 10% 10 year distant recurrence risk will be chosen)
12 months
Feasibility of test in terms of time interval.
Time Frame: 12 months
Time interval between prescription and result of the test (% < 10 days)
12 months
differences in results between local and central reading of ER, PR, Her2 and Ki67
Time Frame: 12 months
A comparison with local evaluation of HR, Her2, and ki-67 will be made
12 months
Change of therapy based on the genomic test findings in a virtual tumour board
Time Frame: 12 months
Choice of therapy in a virtual tumour board based on the genomic test findings
12 months
Evaluation of the cost effectiveness of genomic tests
Time Frame: 5 years
Medico-economic impact based on results of the "Optisoin 01" study
5 years

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UNICANCER

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Roman Rouzier, MD, Institut Curie

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 (ANTICIPATED)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2017

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2018

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 9, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 9, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 15, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UC-0140/1620
  • 2016-A01731-50 (OTHER: Id-RCB)
  • UCBG 2-15 (OTHER: UNICANCER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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