Assessment of Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in ER-positive, Her2-negative Early Breast Cancer (OPTIGEN)
Primary Purpose
ER-positive Her2-negative Early Breast Cancer
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Genomic test
Sponsored by
About this trial
This is an interventional diagnostic trial for ER-positive Her2-negative Early Breast Cancer focused on measuring Breast cancer, ER-positive, Her-2 negative, genomic test
Eligibility Criteria
Inclusion Criteria:
- Woman, Age ≥ 18 years;
- Performance status 0 or 1 (according to World Health Organization criteria);
- 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)
- Fully operated breast cancer including complete resection of breast tumor and adequate axillary surgery;
- Available surgical material (formalin-fixed, paraffin-embedded) for genomic test evaluation;
- ER-positive by immuno-histochemical (>10% cells stained or Allred Score≥4);
- HER2-negative by IHC (score 0 or 1+) and/or fluorescence in situ hybridization/silver in situ hybridization/chemiluminescent in situ hybridization ;
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
- Adequate renal, hepatic, cardiac and hematopoietic functions for a chemotherapy administration;
- Willingness and ability to comply with scheduled visits as well as with test results and chemotherapy decision according to the latest;
- Signed informed consent and Health insurance coverage.
Exclusion Criteria:
- Non operable, bilateral, locally advanced, T4 or metastatic breast cancer;
- HER2 Overexpression, as assessed by 3+ IHC or FISH/SISH/CISH amplification;
- 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;
- Any previous systemic or locoregional treatment for the present breast cancer;
- Documented inherited predisposition with BRCA1/2 or TP53 mutation;
- Previous hormone replacement therapy (HRT) stopped less than 2 weeks before surgery;
- Previous treatment for the present breast cancer;
- Person unable to give informed consent.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Endopredict®
Prosigna®
OncotypeDX®
Mammaprint® assay
Arm Description
genomic test Endopredict® realized on surgery tumour samples
genomic test Prosigna® realized on surgery tumour samples
genomic test OncotypeDX® realized on surgery tumour samples
genomic test Mammaprint® assay realized on surgery tumour samples
Outcomes
Primary Outcome Measures
Comparison of genomic tests clinical utility
Pairwise comparisons between genomic tests in terms of percentage of changes between initial adjuvant chemotherapy decision and final receipt of chemotherapy (yes/no)
Secondary Outcome Measures
Distant disease-free survival in patients who do not receive chemotherapy
5-year distant disease-free survival among the pooled cohort of patients who did not receive chemotherapy
Distant disease-free survival in patients who do not receive chemotherapy based on genomic test result.
5-year distant disease-free survival in patients who did not receive chemotherapy based on genomic test result
Reason for discordant final decision when they occur
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)
Feasibility of test in terms of time interval.
Time interval between prescription and result of the test (% < 10 days)
differences in results between local and central reading of ER, PR, Her2 and Ki67
A comparison with local evaluation of HR, Her2, and ki-67 will be made
Change of therapy based on the genomic test findings in a virtual tumour board
Choice of therapy in a virtual tumour board based on the genomic test findings
Evaluation of the cost effectiveness of genomic tests
Medico-economic impact based on results of the "Optisoin 01" study
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03080428
Brief Title
Assessment of Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in ER-positive, Her2-negative Early Breast Cancer
Acronym
OPTIGEN
Official Title
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.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Withdrawn
Why Stopped
The study has been withdrawn because of lack of funding
Study Start Date
May 2017 (Anticipated)
Primary Completion Date
June 2018 (Anticipated)
Study Completion Date
May 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ER-positive Her2-negative Early Breast Cancer
Keywords
Breast cancer, ER-positive, Her-2 negative, genomic test
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Patients will be identified prior to surgery based on biopsy results. During the post-operative multidisciplinary decision-making meeting, a first therapeutic decision to prescribe or not an adjuvant chemotherapy will be taken according to usual clinical and histopathological markers and official guidelines in use in the center. After the patient has signed the inform consent form, the surgical sample will be sent by the investigator site to a selected genomic platform according to the randomization result.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Endopredict®
Arm Type
Active Comparator
Arm Description
genomic test Endopredict® realized on surgery tumour samples
Arm Title
Prosigna®
Arm Type
Active Comparator
Arm Description
genomic test Prosigna® realized on surgery tumour samples
Arm Title
OncotypeDX®
Arm Type
Active Comparator
Arm Description
genomic test OncotypeDX® realized on surgery tumour samples
Arm Title
Mammaprint® assay
Arm Type
Active Comparator
Arm Description
genomic test Mammaprint® assay realized on surgery tumour samples
Intervention Type
Diagnostic Test
Intervention Name(s)
Genomic test
Intervention Description
genomic test realized on surgery block or formalin-fixed paraffin-embedded slides
Primary Outcome Measure Information:
Title
Comparison of genomic tests clinical utility
Description
Pairwise comparisons between genomic tests in terms of percentage of changes between initial adjuvant chemotherapy decision and final receipt of chemotherapy (yes/no)
Time Frame
At the end of the inclusion period: 12 months
Secondary Outcome Measure Information:
Title
Distant disease-free survival in patients who do not receive chemotherapy
Description
5-year distant disease-free survival among the pooled cohort of patients who did not receive chemotherapy
Time Frame
5 years
Title
Distant disease-free survival in patients who do not receive chemotherapy based on genomic test result.
Description
5-year distant disease-free survival in patients who did not receive chemotherapy based on genomic test result
Time Frame
5 years
Title
Reason for discordant final decision when they occur
Description
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)
Time Frame
12 months
Title
Feasibility of test in terms of time interval.
Description
Time interval between prescription and result of the test (% < 10 days)
Time Frame
12 months
Title
differences in results between local and central reading of ER, PR, Her2 and Ki67
Description
A comparison with local evaluation of HR, Her2, and ki-67 will be made
Time Frame
12 months
Title
Change of therapy based on the genomic test findings in a virtual tumour board
Description
Choice of therapy in a virtual tumour board based on the genomic test findings
Time Frame
12 months
Title
Evaluation of the cost effectiveness of genomic tests
Description
Medico-economic impact based on results of the "Optisoin 01" study
Time Frame
5 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Woman, Age ≥ 18 years;
Performance status 0 or 1 (according to World Health Organization criteria);
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)
Fully operated breast cancer including complete resection of breast tumor and adequate axillary surgery;
Available surgical material (formalin-fixed, paraffin-embedded) for genomic test evaluation;
ER-positive by immuno-histochemical (>10% cells stained or Allred Score≥4);
HER2-negative by IHC (score 0 or 1+) and/or fluorescence in situ hybridization/silver in situ hybridization/chemiluminescent in situ hybridization ;
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
Adequate renal, hepatic, cardiac and hematopoietic functions for a chemotherapy administration;
Willingness and ability to comply with scheduled visits as well as with test results and chemotherapy decision according to the latest;
Signed informed consent and Health insurance coverage.
Exclusion Criteria:
Non operable, bilateral, locally advanced, T4 or metastatic breast cancer;
HER2 Overexpression, as assessed by 3+ IHC or FISH/SISH/CISH amplification;
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;
Any previous systemic or locoregional treatment for the present breast cancer;
Documented inherited predisposition with BRCA1/2 or TP53 mutation;
Previous hormone replacement therapy (HRT) stopped less than 2 weeks before surgery;
Previous treatment for the present breast cancer;
Person unable to give informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roman Rouzier, MD
Organizational Affiliation
Institut Curie
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Assessment of Genomic Test Impact on Shared Decision of Adjuvant Chemotherapy in ER-positive, Her2-negative Early Breast Cancer
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