Ignite Creation Date:
2024-05-05 @ 5:22 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00433589
Status:
COMPLETED
Last Update Posted:
2022-11-17
First Post:
2007-02-08
Brief Title:
Genetic Testing or Clinical Assessment in Determining the Need for Chemotherapy in Women With Breast Cancer That Involves No More Than 3 Lymph Nodes
Sponsor:
European Organisation for Research and Treatment of Cancer - EORTC
Organization:
European Organisation for Research and Treatment of Cancer - EORTC
Study Overview
Official Title:
MINDACT Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy A Prospective Randomized Study Comparing the 70-Gene Signature With the Common Clinical-Pathological Criteria in Selecting Patients for Adjuvant Chemotherapy in Breast Cancer With 0 to 3 Positive Nodes
Status:
COMPLETED
Status Verified Date:
2022-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MINDACT
Brief Summary:
RATIONALE Drugs used in chemotherapy work in different ways to stop the growth of tumor cells either by killing the cells or by stopping them from dividing Giving more than one drug combination chemotherapy may kill more tumor cells Estrogen can cause the growth of breast cancer cells Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells Letrozole may fight breast cancer by lowering the amount of estrogen the body makes Giving chemotherapy and hormone therapy after surgery may kill any tumor cells that remain after surgery It is not yet known whether genetic testing is more effective than clinical assessment in determining the need for chemotherapy in treating breast cancer
PURPOSE This randomized phase III trial is studying genetic testing to see how well it works compared with clinical assessment in determining the need for chemotherapy in women with breast cancer that is either node-negative or involves no more than 3 lymph nodes
PURPOSE This randomized phase III trial is studying genetic testing to see how well it works compared with clinical assessment in determining the need for chemotherapy in women with breast cancer that is either node-negative or involves no more than 3 lymph nodes
Detailed Description:
OBJECTIVES
Primary
Compare a molecular profiling approach 70-gene signature vs usual clinical assessment in assigning adequate risk categories and the need to receive adjuvant chemotherapy or not to breast cancer patients with 0-3 positive lymph nodes
Compare the efficacy and long-term toxicities of docetaxel and capecitabine vs standard anthracycline-based chemotherapy regimens in these patients
Determine the best endocrine treatment strategy ie letrozole for 7 years vs sequential tamoxifen for 2 years followed by letrozole for 5 years in these patients
Secondary
Compare both relative hazard ratio and absolute percentage at 5 years efficacy of these regimens in terms of disease-free survival DFS distant metastasis-free survival DMFS and overall survival OS in these patients
Determine overall estimates of efficacy DFS DMFS OS for each treatment strategy according to clinical-pathological prognosis and molecular prognosis in these patients
Estimate the percentage of patients receiving chemotherapy per each prognostic method
Identify predictive gene expression profiles of clinical responseresistance to anthracycline-based and docetaxel-capecitabine chemotherapy in these patients
Compare novel gene expression signatures predicting clinical response in patients treated with sequential tamoxifen-letrozole vs letrozole alone
Compare the OS distributions in patients treated with these regimens
Compare the early and late toxicities of these regimens in these patients
Evaluate adjuvant endocrine treatment success or failure in the subgroup of postmenopausal patients with endocrine-responsive disease
Compare the safety profile of these two endocrine therapy regimens in these patients
OUTLINE This is a partially randomized open-label prospective multicenter study
Patients with both clinical high-risk CHR and genomic high-risk GHR disease are assigned to receive chemotherapy Patients with both clinical low-risk CLR and genomic low-risk GLR disease do not receive chemotherapy Patients with discordant risk between the 2 decision-making tools standard clinical-pathological criteria vs 70-gene signature criteria are randomized to receive chemotherapy or not Patients with HER-2 positive tumors which have both methods discordant and were randomized to no chemotherapy can receive adjuvant trastuzumab alone or with adjuvant endocrine therapy if hormonal receptor positive if decided by the treating physician Patients with HER-2 positive tumors that are classified low-risk by both methods can receive adjuvant trastuzumab alone or with adjuvant endocrine therapy if hormonal receptor positive if decided by the treating physician and if no issues for trastuzumab reimbursement exist in the investigators country
Chemotherapy Patients are stratified according to participating center risk group GHRCLR vs GLRCHR hormone receptor status estrogen receptor ER positive andor progesterone receptor PR positive vs ER and PR negative age 50 years vs at least 50 years HER2neu status positive vs negative vs unknown method of axillary evaluation sentinel only vs dissection and type of surgery mastectomy vs quadrantectomytumorectomy In case PR is unknown the patient will be stratified to the hormone receptor HR negative group if ER is negative and to the HR positive group if ER is positive
Three randomizations took place
One randomization on the discordant groups where clinical risk did not match genomic risk in treatment decision R-T
One randomization for patients who are candidates for chemotherapy R-C randomization between anthracycline based chemotherapy and taxanecapecitabine chemotherapy
One randomization for patients who are candidates for endocrine therapy R-E randomization between 2 years of tamoxifen followed by 5 years of letrozole and 7 years of letrozole
For the treatment decision randomization patients for whom both methods are discordant will be randomized R-T between chemotherapy-decision-making according to clinical criteria using Adjuvant Online or chemotherapy-decision-making according to genomic prognosis using the 70-gene signature
For the chemotherapy randomization patients are randomized to 1 of 2 treatment arms
Arm I anthracycline-based Patients may receive 1 of the following regimens
FEC 100 Patients receive fluorouracil IV epirubicin hydrochloride IV and cyclophosphamide IV on day 1 Treatment repeats every 3 weeks for 6 courses
Canadian CEF Patients receive oral cyclophosphamide on days 1-14 or IV on days 1 and 8 and epirubicin hydrochloride IV and fluorouracil IV on days 1 and 8 Treatment repeats every 4 weeks for 6 courses
CAF Patients receive cyclophosphamide IV doxorubicin hydrochloride IV and fluorouracil IV on day 1 Treatment repeats every 4 weeks for 6 courses
FAC Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1 and fluorouracil IV on days 1 and 8 Treatment repeats every 3 weeks for 6 courses
E-CMF Patients receive epirubicin hydrochloride IV on day 1 Treatment repeats every 3 weeks for 4 courses Patients then receive cyclophosphamide IV methotrexate IV and fluorouracil IV on days 1 and 8 Treatment repeats every 4 weeks for 4 courses
NOTE Patients who refuse randomization may be treated with another chemotherapy regimen and still be included in the study
Arm II docetaxel and capecitabine Patients receive docetaxel IV over 1 hour on day 1 and oral capecitabine twice daily on days 1-14 Treatment repeats every 3 weeks for 6 courses
For the endocrine therapy randomization all postmenopausal and some premenopausal patients who have endocrine-responsive tumors Patients are stratified according to participating center risk group GHRCHR vs GHRCLR vs GLRCHR vs GLRCLR adjuvant chemotherapy no vs nonrandomized vs arm I vs arm II endocrine sensitivity both ER and PR positive vs either ER or PR positive age 50 years vs at least 50 years HER2neu status positive vs negative vs unknown method of axillary evaluation sentinel only vs dissection and type of surgery mastectomy vs quadrantectomytumorectomy In case PR is unknown the patient will be stratified to the HR negative group if ER is negative and to the HR positive group if ER is positive
Therapy begins after prior surgery in patients who did not receive chemotherapy and after chemotherapy in those who did Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive oral tamoxifen citrate once daily for 2 years Patients then receive oral letrozole once daily for 5 years
Arm II Patients receive oral letrozole once daily for 7 years NOTE The first dose of endocrine therapy should be administered within 4 weeks following the randomization R-E date If treatment has not started within 300 days after definitive surgery the patient becomes ineligible for randomized endocrine therapy
NOTE Premenopausal women 50 years must undergo adequate ovarian suppression gonadotropin releasing hormone bilateral oophorectomy or bilateral ovarian radiation
NOTE Patients who have endocrine-responsive tumors but refuse randomization should receive standard endocrine therapy and may remain on study
After completion of study treatment patients are followed annually for at least 15 years
FINAL ACCRUAL A total of 6694 patients have been accrued for this study
Primary
Compare a molecular profiling approach 70-gene signature vs usual clinical assessment in assigning adequate risk categories and the need to receive adjuvant chemotherapy or not to breast cancer patients with 0-3 positive lymph nodes
Compare the efficacy and long-term toxicities of docetaxel and capecitabine vs standard anthracycline-based chemotherapy regimens in these patients
Determine the best endocrine treatment strategy ie letrozole for 7 years vs sequential tamoxifen for 2 years followed by letrozole for 5 years in these patients
Secondary
Compare both relative hazard ratio and absolute percentage at 5 years efficacy of these regimens in terms of disease-free survival DFS distant metastasis-free survival DMFS and overall survival OS in these patients
Determine overall estimates of efficacy DFS DMFS OS for each treatment strategy according to clinical-pathological prognosis and molecular prognosis in these patients
Estimate the percentage of patients receiving chemotherapy per each prognostic method
Identify predictive gene expression profiles of clinical responseresistance to anthracycline-based and docetaxel-capecitabine chemotherapy in these patients
Compare novel gene expression signatures predicting clinical response in patients treated with sequential tamoxifen-letrozole vs letrozole alone
Compare the OS distributions in patients treated with these regimens
Compare the early and late toxicities of these regimens in these patients
Evaluate adjuvant endocrine treatment success or failure in the subgroup of postmenopausal patients with endocrine-responsive disease
Compare the safety profile of these two endocrine therapy regimens in these patients
OUTLINE This is a partially randomized open-label prospective multicenter study
Patients with both clinical high-risk CHR and genomic high-risk GHR disease are assigned to receive chemotherapy Patients with both clinical low-risk CLR and genomic low-risk GLR disease do not receive chemotherapy Patients with discordant risk between the 2 decision-making tools standard clinical-pathological criteria vs 70-gene signature criteria are randomized to receive chemotherapy or not Patients with HER-2 positive tumors which have both methods discordant and were randomized to no chemotherapy can receive adjuvant trastuzumab alone or with adjuvant endocrine therapy if hormonal receptor positive if decided by the treating physician Patients with HER-2 positive tumors that are classified low-risk by both methods can receive adjuvant trastuzumab alone or with adjuvant endocrine therapy if hormonal receptor positive if decided by the treating physician and if no issues for trastuzumab reimbursement exist in the investigators country
Chemotherapy Patients are stratified according to participating center risk group GHRCLR vs GLRCHR hormone receptor status estrogen receptor ER positive andor progesterone receptor PR positive vs ER and PR negative age 50 years vs at least 50 years HER2neu status positive vs negative vs unknown method of axillary evaluation sentinel only vs dissection and type of surgery mastectomy vs quadrantectomytumorectomy In case PR is unknown the patient will be stratified to the hormone receptor HR negative group if ER is negative and to the HR positive group if ER is positive
Three randomizations took place
One randomization on the discordant groups where clinical risk did not match genomic risk in treatment decision R-T
One randomization for patients who are candidates for chemotherapy R-C randomization between anthracycline based chemotherapy and taxanecapecitabine chemotherapy
One randomization for patients who are candidates for endocrine therapy R-E randomization between 2 years of tamoxifen followed by 5 years of letrozole and 7 years of letrozole
For the treatment decision randomization patients for whom both methods are discordant will be randomized R-T between chemotherapy-decision-making according to clinical criteria using Adjuvant Online or chemotherapy-decision-making according to genomic prognosis using the 70-gene signature
For the chemotherapy randomization patients are randomized to 1 of 2 treatment arms
Arm I anthracycline-based Patients may receive 1 of the following regimens
FEC 100 Patients receive fluorouracil IV epirubicin hydrochloride IV and cyclophosphamide IV on day 1 Treatment repeats every 3 weeks for 6 courses
Canadian CEF Patients receive oral cyclophosphamide on days 1-14 or IV on days 1 and 8 and epirubicin hydrochloride IV and fluorouracil IV on days 1 and 8 Treatment repeats every 4 weeks for 6 courses
CAF Patients receive cyclophosphamide IV doxorubicin hydrochloride IV and fluorouracil IV on day 1 Treatment repeats every 4 weeks for 6 courses
FAC Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1 and fluorouracil IV on days 1 and 8 Treatment repeats every 3 weeks for 6 courses
E-CMF Patients receive epirubicin hydrochloride IV on day 1 Treatment repeats every 3 weeks for 4 courses Patients then receive cyclophosphamide IV methotrexate IV and fluorouracil IV on days 1 and 8 Treatment repeats every 4 weeks for 4 courses
NOTE Patients who refuse randomization may be treated with another chemotherapy regimen and still be included in the study
Arm II docetaxel and capecitabine Patients receive docetaxel IV over 1 hour on day 1 and oral capecitabine twice daily on days 1-14 Treatment repeats every 3 weeks for 6 courses
For the endocrine therapy randomization all postmenopausal and some premenopausal patients who have endocrine-responsive tumors Patients are stratified according to participating center risk group GHRCHR vs GHRCLR vs GLRCHR vs GLRCLR adjuvant chemotherapy no vs nonrandomized vs arm I vs arm II endocrine sensitivity both ER and PR positive vs either ER or PR positive age 50 years vs at least 50 years HER2neu status positive vs negative vs unknown method of axillary evaluation sentinel only vs dissection and type of surgery mastectomy vs quadrantectomytumorectomy In case PR is unknown the patient will be stratified to the HR negative group if ER is negative and to the HR positive group if ER is positive
Therapy begins after prior surgery in patients who did not receive chemotherapy and after chemotherapy in those who did Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive oral tamoxifen citrate once daily for 2 years Patients then receive oral letrozole once daily for 5 years
Arm II Patients receive oral letrozole once daily for 7 years NOTE The first dose of endocrine therapy should be administered within 4 weeks following the randomization R-E date If treatment has not started within 300 days after definitive surgery the patient becomes ineligible for randomized endocrine therapy
NOTE Premenopausal women 50 years must undergo adequate ovarian suppression gonadotropin releasing hormone bilateral oophorectomy or bilateral ovarian radiation
NOTE Patients who have endocrine-responsive tumors but refuse randomization should receive standard endocrine therapy and may remain on study
After completion of study treatment patients are followed annually for at least 15 years
FINAL ACCRUAL A total of 6694 patients have been accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| SANOFI-AVENTIS-EORTC-10041 | EudraCT Number | None | None |
| 2005-002625-31 | EUDRACT_NUMBER | None | None |
| BIG-3-04 | None | None | None |
| EU-20676 | None | None | None |
| NOVARTIS-EORTC-10041 | None | None | None |
| ROCHE-EORTC-10041 | None | None | None |