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

Tracking Information

• First Submitted Date: December 14, 2006
• First Posted Date: December 15, 2006
• Last Update Posted Date: March 24, 2023
• Study Start Date: March 2004
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 20, 2011)

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

• Original Primary Outcome Measures (submitted: December 14, 2006): Bone mineral density measured at 12 months from initiation of therapy

Current Secondary Outcome Measures (submitted: October 20, 2011)

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

Original Secondary Outcome Measures (submitted: December 14, 2006)

• Bone mineral density measured yearly after first year of therapy
• Bone resorption measured with urinary biomarkers yearly
• disease free survival
• overall survival
• toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

Intervention

• 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
• Drug: letrozole
  2.5 mg daily for 5 years
• Drug: zoledronic acid
  4 mg every 6 months

Study Arms

• Active Comparator: A
  Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
  Interventions:

  • Drug: tamoxifen
  • Drug: triptorelin
• Active Comparator: B
  Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
  Interventions:

  • Drug: triptorelin
  • Drug: letrozole
• 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.
  Interventions:

  • Drug: triptorelin
  • Drug: letrozole
  • Drug: zoledronic acid

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 14, 2017): 1294
• Original Enrollment (submitted: December 14, 2006): 500
• Estimated Study Completion Date: November 2024
• Estimated Primary Completion Date: November 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy

Administrative Information

• NCT Number: NCT00412022
• Other Study ID Numbers: HOBOE
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: National Cancer Institute, Naples
• Original Responsible Party: Not Provided
• Current Study Sponsor: National Cancer Institute, Naples
• Original Study Sponsor: Same as current
• Collaborators: 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

• PRS Account: National Cancer Institute, Naples
• Verification Date: March 2023