Back to resultsHOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer. (HOBOE)
Primary Purpose
Breast Cancer
Status
Active
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
tamoxifen
triptorelin
letrozole
zoledronic acid
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer focused on measuring early breast cancer, adjuvant therapy, premenopause, premenopausal, menopausal status, postmenopause, bone mineral density, hormone sensitive, aromatase inhibitors, letrozole, disease-free survival
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
Sites / Locations
- S. Giuseppe Moscati
- Azienda Ospedaliera Treviglio - Caravaggio
- Azienda Ospedaliera G. Rummo
- Ospedale Senatore Antonio Perrino
- Istituto Romagnolo per lo Studio e la Cura dei Tumori
- Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio
- Ospedale Santa Maria Annunziata
- Istituto Nazionale per la ricerca Sul Cancro
- Ospedale Riuniti
- Ospedale Unico della Versilia
- Istituto Nazionale dei Tumori,
- Ospedale Cardarelli
- Seconda Università di Napoli
- Università Federico II, Cattedra di Oncologia Medica
- Casa di Cura La Maddalena
- Ospedale Silvestrini
- Ospedale Santa Chiara
- Università di Sassari
- Ospedale Santa Chiara
- ASL Viterbo Ospedale Belcolle
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Experimental
Arm Label
A
B
C
Arm Description
Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
Outcomes
Primary Outcome Measures
disease free survival in premenopausal patients
bone mineral density
Secondary Outcome Measures
Bone mineral density measured
disease free survival in postmenopausal patients
overall survival
toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients
Full Information
NCT ID
NCT00412022
First Posted
December 14, 2006
Last Updated
March 23, 2023
Sponsor
National Cancer Institute, Naples
Collaborators
University of Campania "Luigi Vanvitelli"
1. Study Identification
Unique Protocol Identification Number
NCT00412022
Brief Title
HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.
Acronym
HOBOE
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
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 2004 (undefined)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
November 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute, Naples
Collaborators
University of Campania "Luigi Vanvitelli"
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
early breast cancer, adjuvant therapy, premenopause, premenopausal, menopausal status, postmenopause, bone mineral density, hormone sensitive, aromatase inhibitors, letrozole, disease-free survival
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1294 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A
Arm Type
Active Comparator
Arm Description
Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
Arm Title
B
Arm Type
Active Comparator
Arm Description
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
Arm Title
C
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
tamoxifen
Intervention Description
20 mg daily for 5 years
Intervention Type
Drug
Intervention Name(s)
triptorelin
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
letrozole
Intervention Description
2.5 mg daily for 5 years
Intervention Type
Drug
Intervention Name(s)
zoledronic acid
Intervention Description
4 mg every 6 months
Primary Outcome Measure Information:
Title
disease free survival in premenopausal patients
Time Frame
observation period is 10 years from initiation of treatment
Title
bone mineral density
Time Frame
12 months from initiation of therapy
Secondary Outcome Measure Information:
Title
Bone mineral density measured
Time Frame
yearly after first year of therapy
Title
disease free survival in postmenopausal patients
Time Frame
observation period is 10 years from initiation of treatment
Title
overall survival
Time Frame
observation period is 10 years from initiation of treatment
Title
toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients
Time Frame
monthly
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea De Matteis, M.D.
Organizational Affiliation
NCI Naples, Division of Medical Oncology C
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ciro Gallo, M.D., Ph.D.
Organizational Affiliation
University of Campania "Luigi Vanvitelli"
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Francesco Perrone, M.D., Ph.D.
Organizational Affiliation
NCI Naples, Clinical Trials Unit
Official's Role
Principal Investigator
Facility Information:
Facility Name
S. Giuseppe Moscati
City
Avellino
State/Province
AV
Country
Italy
Facility Name
Azienda Ospedaliera Treviglio - Caravaggio
City
Treviglio
State/Province
BG
Country
Italy
Facility Name
Azienda Ospedaliera G. Rummo
City
Benevento
State/Province
BN
Country
Italy
Facility Name
Ospedale Senatore Antonio Perrino
City
Brindisi
State/Province
BR
Country
Italy
Facility Name
Istituto Romagnolo per lo Studio e la Cura dei Tumori
City
Meldola
State/Province
FC
Country
Italy
Facility Name
Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio
City
Saronno
State/Province
VA
Country
Italy
Facility Name
Ospedale Santa Maria Annunziata
City
Bagno a Ripoli
Country
Italy
Facility Name
Istituto Nazionale per la ricerca Sul Cancro
City
Genova
Country
Italy
Facility Name
Ospedale Riuniti
City
Livorno
Country
Italy
Facility Name
Ospedale Unico della Versilia
City
Lucca
Country
Italy
Facility Name
Istituto Nazionale dei Tumori,
City
Napoli
Country
Italy
Facility Name
Ospedale Cardarelli
City
Napoli
Country
Italy
Facility Name
Seconda Università di Napoli
City
Napoli
Country
Italy
Facility Name
Università Federico II, Cattedra di Oncologia Medica
City
Napoli
Country
Italy
Facility Name
Casa di Cura La Maddalena
City
Palermo
Country
Italy
Facility Name
Ospedale Silvestrini
City
Perugia
Country
Italy
Facility Name
Ospedale Santa Chiara
City
Pisa
Country
Italy
Facility Name
Università di Sassari
City
Sassari
Country
Italy
Facility Name
Ospedale Santa Chiara
City
Trento
Country
Italy
Facility Name
ASL Viterbo Ospedale Belcolle
City
Viterbo
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
19380451
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.
Results Reference
result
PubMed Identifier
18086795
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.
Results Reference
result
PubMed Identifier
22412041
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.
Results Reference
result
PubMed Identifier
31164265
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.
Results Reference
derived
Learn more about this trial
HOBOE: A Phase 3 Study of Adjuvant Triptorelin and Tamoxifen, Letrozole, or Letrozole and Zoledronic Acid in Premenopausal Patients With Breast Cancer.
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