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

Breast Cancer Clinical Trial

— 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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00412022
• Other study ID #: HOBOE
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 2004
• Est. completion date: November 2024

Study information

• Verified date: March 2023
• Source: National Cancer Institute, Naples
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1294
• Est. completion date: November 2024
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Italy	S. Giuseppe Moscati	Avellino	AV
Italy	Ospedale Santa Maria Annunziata	Bagno a Ripoli
Italy	Azienda Ospedaliera G. Rummo	Benevento	BN
Italy	Ospedale Senatore Antonio Perrino	Brindisi	BR
Italy	Istituto Nazionale per la ricerca Sul Cancro	Genova
Italy	Ospedale Riuniti	Livorno
Italy	Ospedale Unico della Versilia	Lucca
Italy	Istituto Romagnolo per lo Studio e la Cura dei Tumori	Meldola	FC
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	Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio	Saronno	VA
Italy	Università di Sassari	Sassari
Italy	Ospedale Santa Chiara	Trento
Italy	Azienda Ospedaliera Treviglio - Caravaggio	Treviglio	BG
Italy	ASL Viterbo Ospedale Belcolle	Viterbo

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute, Naples	University of Campania "Luigi Vanvitelli"

Country where clinical trial is conducted

Italy, 

References & Publications (3)

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 Laurentii — View 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 com — View 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 compar — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease free survival in premenopausal patients		observation period is 10 years from initiation of treatment
Primary	bone mineral density		12 months from initiation of therapy
Secondary	Bone mineral density measured		yearly after first year of therapy
Secondary	disease free survival in postmenopausal patients		observation period is 10 years from initiation of treatment
Secondary	overall survival		observation period is 10 years from initiation of treatment
Secondary	toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients		monthly