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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Cancer Institute, Naples
Sponsor:
Collaborator:
Second University of Naples
Information provided by (Responsible Party):
National Cancer Institute, Naples
ClinicalTrials.gov Identifier:
NCT00412022
First received: December 14, 2006
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: tamoxifen
Drug: triptorelin
Drug: letrozole
Drug: zoledronic acid
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute, Naples:

Primary Outcome Measures:
  • disease free survival in premenopausal patients [ Time Frame: observation period is 10 years from initiation of treatment ] [ Designated as safety issue: No ]
  • bone mineral density [ Time Frame: 12 months from initiation of therapy ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bone mineral density measured [ Time Frame: yearly after first year of therapy ] [ Designated as safety issue: No ]
  • disease free survival in postmenopausal patients [ Time Frame: observation period is 10 years from initiation of treatment ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: observation period is 10 years from initiation of treatment ] [ Designated as safety issue: No ]
  • toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients [ Time Frame: monthly ] [ Designated as safety issue: No ]

Estimated Enrollment: 1050
Study Start Date: March 2004
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A
Triptorelin 3.75 mg IM every 4 weeks and Tamoxifen 20 mg daily, for 5 years
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
Active Comparator: B
Triptorelin 3.75 mg IM every 4 weeks and Letrozole 2.5 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
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.
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00412022

Contacts
Contact: Francesco Perrone, M.D., Ph.D +39 081 5903 ext 571 francesco.perrone@usc-intnapoli.net
Contact: Massimo Di Maio, M.D. +39 081 5903 ext 383 massimo.dimaio@usc-intnapoli.net

Locations
Italy
S. Giuseppe Moscati Recruiting
Avellino, AV, Italy
Azienda Ospedaliera Treviglio - Caravaggio Recruiting
Treviglio, BG, Italy
Azienda Ospedaliera G. Rummo Recruiting
Benevento, BN, Italy
Ospedale Senatore Antonio Perrino Recruiting
Brindisi, BR, Italy
Istituto Romagnolo per lo Studio e la Cura dei Tumori Recruiting
Meldola, FC, Italy
Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio Recruiting
Saronno, VA, Italy
Ospedale Santa Maria Annunziata Recruiting
Bagno a Ripoli, Italy
Istituto Nazionale per la ricerca Sul Cancro Recruiting
Genova, Italy
Ospedale Riuniti Recruiting
Livorno, Italy
Ospedale Unico della Versilia Recruiting
Lucca, Italy
Ospedale Cardarelli Recruiting
Napoli, Italy
Università Federico II, Cattedra di Oncologia Medica Recruiting
Napoli, Italy
Istituto Nazionale dei Tumori, Recruiting
Napoli, Italy
Seconda Università di Napoli Recruiting
Napoli, Italy
Casa di Cura La Maddalena Recruiting
Palermo, Italy
Ospedale Silvestrini Recruiting
Perugia, Italy
Ospedale Santa Chiara Recruiting
Pisa, Italy
Università di Sassari Recruiting
Sassari, Italy
Ospedale Santa Chiara Recruiting
Trento, Italy
ASL Viterbo Ospedale Belcolle Recruiting
Viterbo, Italy
Sponsors and Collaborators
National Cancer Institute, Naples
Second University of Naples
Investigators
Principal Investigator: Andrea De Matteis, M.D. NCI Naples, Division of Medical Oncology C
Principal Investigator: Ciro Gallo, M.D., Ph.D. Second University of Naples
Principal Investigator: Francesco Perrone, M.D., Ph.D. NCI Naples, Clinical Trials Unit
  More Information

Publications:
Responsible Party: National Cancer Institute, Naples
ClinicalTrials.gov Identifier: NCT00412022     History of Changes
Other Study ID Numbers: HOBOE
Study First Received: December 14, 2006
Last Updated: February 20, 2014
Health Authority: Italy: Ethics Committee

Keywords provided by National Cancer Institute, Naples:
adjuvant therapy
menopausal status
postmenopause
hormone sensitive
early breast cancer
premenopause
premenopausal
bone mineral density
aromatase inhibitors
letrozole
disease-free survival

Additional relevant MeSH terms:
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Tamoxifen
Triptorelin Pamoate
Zoledronic acid
Diphosphonates
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bone Density Conservation Agents
Physiological Effects of Drugs
Estrogen Antagonists
Estrogen Receptor Modulators
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Luteolytic Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on September 18, 2014