Clinical trial NCT00412022: HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: early breast cancer
adjuvant therapy
premenopause
premenopausal
menopausal status
postmenopause
bone mineral density
hormone sensitive
aromatase inhibitors
letrozole
disease-free survival
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
Collaborators: name: University of Campania Luigi Vanvitelli
First posted: 2006-12-15
Enrollment: 1294
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: disease free survival in premenopausal patients
timeFrame: observation period is 10 years from initiation of treatment
measure: bone mineral density
timeFrame: 12 months from initiation of therapy
Secondary outcomes:
measure: Bone mineral density measured
timeFrame: yearly after first year of therapy
measure: disease free survival in postmenopausal patients
timeFrame: observation period is 10 years from initiation of treatment
measure: overall survival
timeFrame: observation period is 10 years from initiation of treatment
measure: toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients
timeFrame: monthly
Other outcomes:
Locations:
city: Avellino
country: Italy
facility: S. Giuseppe Moscati
state: AV
city: Treviglio
country: Italy
facility: Azienda Ospedaliera Treviglio - Caravaggio
state: BG
city: Benevento
country: Italy
facility: Azienda Ospedaliera G. Rummo
state: BN
city: Brindisi
country: Italy
facility: Ospedale Senatore Antonio Perrino
state: BR
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio e la Cura dei Tumori
state: FC
city: Saronno
country: Italy
facility: Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio
state: VA
city: Bagno a Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata
city: Genova
country: Italy
facility: Istituto Nazionale per la ricerca Sul Cancro
city: Livorno
country: Italy
facility: Ospedale Riuniti
city: Lucca
country: Italy
facility: Ospedale Unico della Versilia
city: Napoli
country: Italy
facility: Istituto Nazionale dei Tumori,
city: Napoli
country: Italy
facility: Ospedale Cardarelli
city: Napoli
country: Italy
facility: Seconda Università di Napoli
city: Napoli
country: Italy
facility: Università Federico II, Cattedra di Oncologia Medica
city: Palermo
country: Italy
facility: Casa di Cura La Maddalena
city: Perugia
country: Italy
facility: Ospedale Silvestrini
city: Pisa
country: Italy
facility: Ospedale Santa Chiara
city: Sassari
country: Italy
facility: Università di Sassari
city: Trento
country: Italy
facility: Ospedale Santa Chiara
city: Viterbo
country: Italy
facility: ASL Viterbo Ospedale Belcolle
Study officials:
affiliation: NCI Naples, Division of Medical Oncology C
name: Andrea De Matteis, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Campania Luigi Vanvitelli
name: Ciro Gallo, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: NCI Naples, Clinical Trials Unit
name: Francesco Perrone, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. doi: 10.1200/JCO.2007.13.5319. Epub 2007 Dec 17.
citation: 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):2027-2033. doi: 10.1093/annonc/mdr600. Epub 2012 Mar 12.
citation: Perrone F, De Laurentiis M, De Placido S, Orditura M, Cinieri S, Riccardi F, Ribecco AS, Putzu C, Del Mastro L, Rossi E, Tinessa V, Mosconi AM, Nuzzo F, Di Rella F, Gravina A, Iodice G, Landi G, Pacilio C, Forestieri V, Lauria R, Fabbri A, Ibrahim T, De Maio E, Barni S, Gori S, Simeon V, Arenare L, Daniele G, Piccirillo MC, Normanno N, de Matteis A, Gallo C. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial. Eur J Cancer. 2019 Sep;118:178-186. doi: 10.1016/j.ejca.2019.05.004. Epub 2019 Jun 1.