HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.

Study Overview
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Brief Summary
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The HOBOE study was amended in November 2009, and, after reaching enrollment of the first 500 patients, the study began recruiting premenopausal patients only. The primary objective of the extended study is to compare disease free survival in premenopausal patients with early breast cancer. Patients receive triptorelin and are randomized in a 1:1:1 fashion to receive tamoxifen or letrozole, or letrozole + zoledronic acid. The purpose of the HOBOE study, Version 1, was to compare the adjuvant hormonal therapy treatments of Tamoxifen, Letrozole and Letrozole + Zoledronate for their effects on bone loss in breast cancer patients. Postmenopausal and premenopausal patients were eligible, the latter also receiving monthly triptorelin. Upon reaching the enrollment of the first 500 patients in March 2010, the study began recruiting premenopausal patients only.

Official Title
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Phase III Randomized Study of the Effects on Bone Mineral Density of Tamoxifen, Letrozole, and Letrozole + Zoledronic Acid as Adjuvant Treatment of Patients With Early Breast Cancer; VERSION 2 AMENDED Phase 3 Study of Triptorelin and Tamoxifen, Letrozole, or Letrozole + Zoledronic Acid in Adjuvant Treatment of Premenopausal Endocrine Responsive Breast Cancer Patients.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: tamoxifen
* Drug: triptorelin
* Drug: letrozole
* Drug: zoledronic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological diagnosis of breast cancer Surgical resection of breast cancer (breast conserving surgery or mastectomy) No evidence of disease Indication for adjuvant hormonal therapy (ER and/or PgR positive with IHC exam in at least 1% of primary tumor cells, according to St. Gallen criteria) Patient age at least 18 years Written informed consent . Premenopausal status defined as LMP within 12 months of randomization (FSH, LH will not be considered as determinants of menopausal status due the chemotherapy induced reversible ovarian suppression) Please note that patients who have received neoadjuvant or adjuvant chemotherapy and/or locoregional radiation therapy may be included in the study Exclusion Criteria: Performance status (ECOG)>2. Previous or concomitant malignancy (with the exception of adequately treated nonmalignant skin cancer and carcinoma in situ of the uterine cervix Metastatic breast cancer Creatinine > 1.25 times the value of upper normal limit Pregnant or lactating females Clinical or radiologic evidence of bone fractures Treatment with systemic cortisone therapy within 12 months prior to randomization Treatment with drugs that could alter bone metabolism (calcitonin, mithramycin, gallium nitrate) within 2 weeks prior to randomization Previous treatment with tamoxifen or aromatase inhibitors AST and/or ALT > 3 times the value of upper normal limit with clinical and laboratory findings that indicate a grade of hepatic insufficiency that could potentially increase the risk of assuming letrozole Any concomitant conditions that would, in the Investigator's opinion, contraindicate the use of any of the drugs used in this study Inability to provide informed consent Inability to comply with followup Patient undergoing invasive dental work at time of baseline evaluation or foreseen during the course of adjuvant therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years | Drug: tamoxifen<br>* 20 mg daily for 5 years<br>Drug: triptorelin<br>* Premenopausal patients will receive triptorelin 3.75 mg IM at the beginning of therapy and every 4 weeks for 5 years or up to age 55<br>|
| Active Comparator: B<br>Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years | Drug: triptorelin<br>* Premenopausal patients will receive triptorelin 3.75 mg IM at the beginning of therapy and every 4 weeks for 5 years or up to age 55<br>Drug: letrozole<br>* 2.5 mg daily for 5 years<br>|
| Experimental: C<br>Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months. | Drug: triptorelin<br>* Premenopausal patients will receive triptorelin 3.75 mg IM at the beginning of therapy and every 4 weeks for 5 years or up to age 55<br>Drug: letrozole<br>* 2.5 mg daily for 5 years<br>Drug: zoledronic acid<br>* 4 mg every 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival in premenopausal patients |  | observation period is 10 years from initiation of treatment | 
| bone mineral density |  | 12 months from initiation of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone mineral density measured |  | yearly after first year of therapy | 
| disease free survival in postmenopausal patients |  | observation period is 10 years from initiation of treatment | 
| overall survival |  | observation period is 10 years from initiation of treatment | 
| toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients |  | monthly | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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premenopause, premenopausal, menopausal status, postmenopause, bone mineral density, hormone sensitive, aromatase inhibitors, letrozole, disease-free survival, adjuvant therapy, early breast cancer