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

National Cancer Institute, Naples

Status and phase: Active, not recruiting; Phase 3

Conditions: Breast Cancer

Treatments: Drug: triptorelin; Drug: zoledronic acid; Drug: tamoxifen; Drug: letrozole

Study type: Interventional

Funder types: Other

Identifiers

NCT00412022

HOBOE

Details and patient eligibility

About

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.

Enrollment: 1,294 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,294 participants in 3 patient groups

A

Active Comparator group

Description:

Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years

Treatment:

Drug: triptorelin

Drug: tamoxifen

B

Active Comparator group

Description:

Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years

Treatment:

Drug: triptorelin

Drug: letrozole

C

Experimental group

Description:

Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.

Treatment:

Drug: zoledronic acid

Drug: triptorelin

Drug: letrozole