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

Condition(s) targeted: Breast Cancer

Intervention: tamoxifen (Drug); triptorelin (Drug); letrozole (Drug); zoledronic acid (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Cancer Institute, Naples

Official(s) and/or principal investigator(s):
Andrea De Matteis, M.D., Principal Investigator, Affiliation: NCI Naples, Division of Medical Oncology C
Ciro Gallo, M.D., Ph.D., Principal Investigator, Affiliation: Second University of Naples
Francesco Perrone, M.D., Ph.D., Principal Investigator, Affiliation: NCI Naples, Clinical Trials Unit

Overall contact:
Francesco Perrone, M.D., Ph.D, Phone: +39 081 5903, Ext: 571, Email: francesco.perrone@usc-intnapoli.net

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.

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

disease free survival in premenopausal patients

bone mineral density

Secondary outcome:

Bone mineral density measured

disease free survival in postmenopausal patients

overall survival

toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Female.

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

Francesco Perrone, M.D., Ph.D, Phone: +39 081 5903, Ext: 571, Email: francesco.perrone@usc-intnapoli.net

Ospedale Santa Maria Annunziata, Bagno a Ripoli, Italy; Recruiting

Istituto Nazionale per la ricerca Sul Cancro, Genova, Italy; Recruiting

Ospedale Riuniti, Livorno, Italy; Recruiting

Ospedale Unico della Versilia, Lucca, Italy; Recruiting

Ospedale Cardarelli, Napoli, Italy; Recruiting

Università Federico II, Cattedra di Oncologia Medica, Napoli, Italy; Recruiting

Istituto Nazionale dei Tumori,, Napoli, Italy; Recruiting

Seconda Università di Napoli, Napoli, Italy; Recruiting

Casa di Cura La Maddalena, Palermo, Italy; Recruiting

Ospedale Silvestrini, Perugia, Italy; Recruiting

Ospedale Santa Chiara, Pisa, Italy; Recruiting

Università di Sassari, Sassari, Italy; Recruiting

Ospedale Santa Chiara, Trento, Italy; Recruiting

ASL Viterbo Ospedale Belcolle, Viterbo, Italy; Recruiting

S. Giuseppe Moscati, Avellino, AV, Italy; Recruiting

Azienda Ospedaliera Treviglio - Caravaggio, Treviglio, BG, Italy; Recruiting

Azienda Ospedaliera G. Rummo, Benevento, BN, Italy; Recruiting

Ospedale Senatore Antonio Perrino, Brindisi, BR, Italy; Recruiting

Istituto Romagnolo per lo Studio e la Cura dei Tumori, Meldola, FC, Italy; Recruiting

Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio, Saronno, VA, Italy; Recruiting

Starting date: March 2004
Last updated: January 15, 2013