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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-004216-31 | EudraCT Number |
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| Name | Class |
|---|---|
| National Cancer Institute, France | OTHER_GOV |
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RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using anastrozole may fight breast cancer by lowering the amount of estrogen the body makes. Fulvestrant may fight breast cancer by blocking the use of estrogen by the tumor cells. Given the lack of clinical data on fulvestrant in patients with large operable or locally advanced hormone-receptor-positive breast cancer, and the potential to identify differences in the mechanism of resistance using the neoadjuvant model,we decided to perform a multicentre randomised phase II clinical trial of anastrozole and fulvestrant.
PURPOSE: The aim of this study was to assess the efficacy of neoadjuvant anastrozole and fulvestrant treatment of large operable or locally advanced hormone-receptor-positive breast cancer not eligible for initial breast-conserving surgery, and to identify genomic changes occurring after treatment.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a non-comparative multicentre randomised phase II study in which patients from three French centres were randomly assigned in a 1 : 1 ratio to receive either anatrozole or fulvestrant.
All patients undergo biopsy at baseline. Patients are randomized between the two treatment arms.
Within 8 days after completion of hormone therapy, all patients undergo surgical resection of the residual lesion followed by radiotherapy. Patients then receive oral anastrozole once daily for 5 years.
Tissue samples from biopsy and surgery are analyzed to assess molecular signatures and sensitivity to treatment, and to compare gene expression variation with response.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (ANA) | Active Comparator | Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months. |
|
| Arm B (FULV) | Experimental | Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| anastrozole | Drug | Given orally |
| |
| fulvestrant |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) Determined by Clinical Palpation | Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). | 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) Determined by Ultrasound | Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). |
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DISEASE CHARACTERISTICS:
Histologically confirmed invasive breast cancer, meeting 1 of the following criteria:
T2 (2-5 cm), T3, or T4B, and N0-1 disease
No metastatic disease
Breast lesion not amenable to breast-conserving resection
No inflammatory breast cancer
No prior breast cancer
Hormone receptor status:
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Louis Mauriac, MD | Institut Bergonié | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut Bergonie | Bordeaux | 33076 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26171933 | Result | Quenel-Tueux N, Debled M, Rudewicz J, MacGrogan G, Pulido M, Mauriac L, Dalenc F, Bachelot T, Lortal B, Breton-Callu C, Madranges N, de Lara CT, Fournier M, Bonnefoi H, Soueidan H, Nikolski M, Gros A, Daly C, Wood H, Rabbitts P, Iggo R. Clinical and genomic analysis of a randomised phase II study evaluating anastrozole and fulvestrant in postmenopausal patients treated for large operable or locally advanced hormone-receptor-positive breast cancer. Br J Cancer. 2015 Aug 11;113(4):585-94. doi: 10.1038/bjc.2015.247. Epub 2015 Jul 14. | |
| 32001832 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (ANA) | Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months. anastrozole: Given orally |
| FG001 | Arm B (FULV) | Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months. fulvestrant: Given intramuscularly |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A (ANA) | Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months. anastrozole: Given orally |
| BG001 | Arm B (FULV) | Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months. fulvestrant: Given intramuscularly |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Objective Response Rate (ORR) Determined by Clinical Palpation | Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A (ANA) | Patients receive oral anastrozole as 1 mg film-coated tablets, once daily for 6 months. anastrozole: Given orally |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Clear cell kidney cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (5.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0 = constitutional symptoms |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Nathalie Quenel-Tueux | Institut Bergonié, Medical Oncology department | 05.56.33.33.33 | N.Quenel-Tueux@bordeaux.unicancer.fr |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077384 | Anastrozole |
| D000077267 | Fulvestrant |
| ID | Term |
|---|---|
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 |
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| Drug |
Given intramuscularly |
|
| 6 months |
| Objective Response Rate (ORR) Determined by Mammography | Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). | 6 months |
| Rate of Breast-conserving Surgery | breast-conserving surgery concerns patients who did not undergo mastectomy. | 6 months |
| Percentage of Participants With 5-year Relapse-Free Survival | Relapse-Free survival (RFS) is measured from the date of randomization to the date of the following events, whichever occurs first according to the DATECAN recommendations for breast cancer:
Participants who did not experience events were censored at the date of last follow-up. RFS was estimated using the Kaplan-Meier method. No comparison test was performed between the two arms as this study is non-comparative. | 5 years |
| Derived |
| Lerebours F, Pulido M, Fourme E, Debled M, Becette V, Bonnefoi H, Rivera S, MacGrogan G, Mouret-Reynier MA, de Lara CT, Pierga JY, Breton-Callu C, Venat-Bouvet L, Mathoulin-Pelissier S, de la Motte Rouge T, Dalenc F, Sigal B, Bachelot T, Lemonnier J, Quenel-Tueux N. Predictive factors of 5-year relapse-free survival in HR+/HER2- breast cancer patients treated with neoadjuvant endocrine therapy: pooled analysis of two phase 2 trials. Br J Cancer. 2020 Mar;122(6):759-765. doi: 10.1038/s41416-020-0733-x. Epub 2020 Jan 31. |
| Withdrawal by Subject |
|
| Lost to Follow-up |
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Objective Response Rate (ORR) Determined by Ultrasound | Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). | Out of 108 patients (56 arm A + 52 arm B) evaluable for efficacy ("completed" in flow chart) : 19 patients in Arm A and 31 in arm B with missing size at ultrasound examination | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months |
|
|
|
| Secondary | Objective Response Rate (ORR) Determined by Mammography | Objective response rate is defined as the rate of participants with partial or complete responses according to RECIST V1.0. Complete response is defined as the disappearance of all target lesions and partial response is defined as at least a 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD (RECIST V1.0.). | Out of 108 patients (56 arm A + 52 arm B) evaluable for efficacy ("completed" in flow chart) : 33 patients in Arm A and 34 in arm B with missing size at mammography. | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months |
|
|
|
| Secondary | Rate of Breast-conserving Surgery | breast-conserving surgery concerns patients who did not undergo mastectomy. | Posted | Number | 95% Confidence Interval | percentage of participants | 6 months |
|
|
|
| Secondary | Percentage of Participants With 5-year Relapse-Free Survival | Relapse-Free survival (RFS) is measured from the date of randomization to the date of the following events, whichever occurs first according to the DATECAN recommendations for breast cancer:
Participants who did not experience events were censored at the date of last follow-up. RFS was estimated using the Kaplan-Meier method. No comparison test was performed between the two arms as this study is non-comparative. | Posted | Number | 95% Confidence Interval | Percentage of participants | 5 years |
|
|
|
| 6 |
| 60 |
| 2 |
| 60 |
| 48 |
| 60 |
| EG001 | Arm B (FULV) | Patients receive fulvestrant intramuscularly ( 250 mg/5 ml solution) on days 1, 14, and 28 and then once a month thereafter until 6 months. fulvestrant: Given intramuscularly | 6 | 58 | 3 | 58 | 43 | 58 |
| Bronchial infection | Infections and infestations | CTCAE (5.0) | Systematic Assessment |
|
| Ankle fracture | Injury, poisoning and procedural complications | CTCAE (5.0) | Systematic Assessment |
|
| Endometrial atrophy | Reproductive system and breast disorders | CTCAE (5.0) | Systematic Assessment |
|
| Programmed peritoneal dialysis | Renal and urinary disorders | CTCAE (5.0) | Systematic Assessment |
|
|
| Weight gain | Investigations | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0= Constitutional symptoms |
|
| Injection site reaction | General disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0= Dermatology/Skin |
|
| Hot flashes | Vascular disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0=Endocrine gastrointestinal |
|
| Nausea | Gastrointestinal disorders | CTCAE (5.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0= Neurology |
|
| Agitation | Psychiatric disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0=Neurology / AE term CTCAE V3.0= Mood alteration |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0=PAIN |
|
| MYALGIA | Musculoskeletal and connective tissue disorders | CTCAE (5.0) | Systematic Assessment | SOC CTCAE V3.0= PAIN |
|
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| D017437 |
| Skin and Connective Tissue Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004958 | Estradiol |
| D004963 | Estrenes |
| D004962 | Estranes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D045166 | Estradiol Congeners |
| D012739 | Gonadal Steroid Hormones |
| D042341 | Gonadal Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |