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

Phase 3
Active, not recruiting
Conditions
Breast Cancer
Interventions
Registration Number
NCT00412022
Lead Sponsor
National Cancer Institute, Naples
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 available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
1294
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CletrozoleTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
AtamoxifenTriptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
AtriptorelinTriptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
BtriptorelinTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
BletrozoleTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily, for 5 years
CtriptorelinTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
Czoledronic acidTriptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 mg daily for 5 years + zoledronic acid 4 mg every 6 months.
Primary Outcome Measures
NameTimeMethod
disease free survival in premenopausal patientsobservation period is 10 years from initiation of treatment
bone mineral density12 months from initiation of therapy
Secondary Outcome Measures
NameTimeMethod
Bone mineral density measuredyearly after first year of therapy
overall survivalobservation period is 10 years from initiation of treatment
toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patientsmonthly
disease free survival in postmenopausal patientsobservation period is 10 years from initiation of treatment

Trial Locations

Locations (19)

Istituto Nazionale per la ricerca Sul Cancro

🇮🇹

Genova, Italy

Ospedale Santa Chiara

🇮🇹

Trento, Italy

Ospedale Unico della Versilia

🇮🇹

Lucca, 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

Ospedale Santa Maria Annunziata

🇮🇹

Bagno a Ripoli, 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 Riuniti

🇮🇹

Livorno, 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

Università di Sassari

🇮🇹

Sassari, Italy

ASL Viterbo Ospedale Belcolle

🇮🇹

Viterbo, Italy

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