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

• ClinicalTrials.gov Identifier: NCT00412022
• Recruitment Status: Active, not recruiting
• First Posted: December 15, 2006
• Last Update Posted: March 24, 2023
• Sponsor: National Cancer Institute, Naples
• Collaborator: University of Campania "Luigi Vanvitelli"
• Information provided by (Responsible Party): National Cancer Institute, Naples

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: tamoxifen; Drug: triptorelin; Drug: letrozole; Drug: zoledronic acid	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1294 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: March 2004
• Estimated Primary Completion Date: November 2024
• Estimated Study Completion Date: November 2024

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: A; Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years	Drug: tamoxifen; 20 mg daily for 5 years; Drug: triptorelin; 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
Active Comparator: B; Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years	Drug: triptorelin; 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; Drug: letrozole; 2.5 mg daily for 5 years
Experimental: C; 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; 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; Drug: letrozole; 2.5 mg daily for 5 years; Drug: zoledronic acid; 4 mg every 6 months

Outcome Measures

Primary Outcome Measures :

1. disease free survival in premenopausal patients [ Time Frame: observation period is 10 years from initiation of treatment ]
2. bone mineral density [ Time Frame: 12 months from initiation of therapy ]

Secondary Outcome Measures :

1. Bone mineral density measured [ Time Frame: yearly after first year of therapy ]
2. disease free survival in postmenopausal patients [ Time Frame: observation period is 10 years from initiation of treatment ]
3. overall survival [ Time Frame: observation period is 10 years from initiation of treatment ]
4. toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients [ Time Frame: monthly ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Italy

S. Giuseppe Moscati

Avellino, AV, Italy

Azienda Ospedaliera Treviglio - Caravaggio

Treviglio, BG, Italy

Azienda Ospedaliera G. Rummo

Benevento, BN, Italy

Ospedale Senatore Antonio Perrino

Brindisi, BR, Italy

Istituto Romagnolo per lo Studio e la Cura dei Tumori

Meldola, FC, Italy

Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio

Saronno, VA, Italy

Ospedale Santa Maria Annunziata

Bagno a Ripoli, Italy

Istituto Nazionale per la ricerca Sul Cancro

Genova, Italy

Ospedale Riuniti

Livorno, Italy

Ospedale Unico della Versilia

Lucca, Italy

Istituto Nazionale dei Tumori,

Napoli, Italy

Ospedale Cardarelli

Napoli, Italy

Seconda Università di Napoli

Napoli, Italy

Università Federico II, Cattedra di Oncologia Medica

Napoli, Italy

Casa di Cura La Maddalena

Palermo, Italy

Ospedale Silvestrini

Perugia, Italy

Ospedale Santa Chiara

Pisa, Italy

Università di Sassari

Sassari, Italy

Ospedale Santa Chiara

Trento, Italy

ASL Viterbo Ospedale Belcolle

Viterbo, Italy

Sponsors and Collaborators

National Cancer Institute, Naples

University of Campania "Luigi Vanvitelli"

Investigators

• Principal Investigator: Andrea De Matteis, M.D.; NCI Naples, Division of Medical Oncology C
• Principal Investigator: Ciro Gallo, M.D., Ph.D.; University of Campania "Luigi Vanvitelli"
• Principal Investigator: Francesco Perrone, M.D., Ph.D.; NCI Naples, Clinical Trials Unit

More Information

Publications of Results:

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. doi: 10.1200/JCO.2007.13.5319. 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):2027-2033. doi: 10.1093/annonc/mdr600. Epub 2012 Mar 12.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: National Cancer Institute, Naples
• ClinicalTrials.gov Identifier: NCT00412022
• Other Study ID Numbers: HOBOE
• First Posted: December 15, 2006
• Last Update Posted: March 24, 2023
• Last Verified: March 2023

Keywords provided by National Cancer Institute, Naples:

early breast cancer; adjuvant therapy; premenopause; premenopausal; menopausal status; postmenopause; bone mineral density; hormone sensitive; aromatase inhibitors; letrozole; disease-free survival

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Tamoxifen; Zoledronic Acid; Letrozole; Triptorelin Pamoate; Antineoplastic Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Bone Density Conservation Agents; Luteolytic Agents; Contraceptive Agents, Female; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Hormonal