Breast Cancer | HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.
Breast Cancer research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:tamoxifen20 mg daily for 5 years
Drug:triptorelinPremenopausal 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
Drug:letrozole2.5 mg daily for 5 years
Drug:zoledronic acid4 mg every 6 months
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
ATriptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
BTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
CTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
Active, not recruiting
Start Date: March 2004
Completed Date: March 2019
Phase: Phase 3
Primary Outcome: disease free survival in premenopausal patients
Secondary Outcome: Bone mineral density measured
Study sponsors, principal investigator, and references
Principal Investigator: Andrea De Matteis, M.D.
Lead Sponsor: National Cancer Institute, Naples
Collaborator: University of Campania "Luigi Vanvitelli"
Rossi E, Morabito A, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, De Maio E, Di Maio M, Piccirillo MC, De Feo G, D'Aiuto G, Botti G, Chiodini P, Gallo C, Perrone F, de Matteis A. Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial. J Clin Oncol. 2009 Jul 1;27(19):3192-7. doi: 10.1200/JCO.2008.18.6213. Epub 2009 Apr 20.
Rossi E, Morabito A, De Maio E, Di Rella F, Esposito G, Gravina A, Labonia V, Landi G, Nuzzo F, Pacilio C, Piccirillo MC, D'Aiuto G, D'Aiuto M, Rinaldo M, Botti G, Gallo C, Perrone F, de Matteis A. Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer. J Clin Oncol. 2008 Jan 10;26(2):264-70. Epub 2007 Dec 17.
Nuzzo F, Gallo C, Lastoria S, Di Maio M, Piccirillo MC, Gravina A, Landi G, Rossi E, Pacilio C, Labonia V, Di Rella F, Bartiromo A, Buonfanti G, De Feo G, Esposito G, D'Aniello R, Maiolino P, Signoriello S, De Maio E, Tinessa V, Colantuoni G, De Laurentiis M, D'Aiuto M, Di Bonito M, Botti G, Giordano P, Daniele G, Morabito A, Normanno N, de Matteis A, Perrone F. Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study. Ann Oncol. 2012 Aug;23(8):2027-33. doi: 10.1093/annonc/mdr600. Epub 2012 Mar 12.