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

Sponsor

National Cancer Institute, Naples (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00412022

Collaborator

University of Campania "Luigi Vanvitelli" (Other)

1,294

Enrollment

Locations

Arms

224

Duration (Months)

64.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: tamoxifen Drug: triptorelin Drug: letrozole Drug: zoledronic acid	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

1294 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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.

Study Start Date :

Mar 1, 2004

Anticipated Primary Completion Date :

Nov 1, 2021

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

disease free survival in premenopausal patients [observation period is 10 years from initiation of treatment]
bone mineral density [12 months from initiation of therapy]

Secondary Outcome Measures

Bone mineral density measured [yearly after first year of therapy]
disease free survival in postmenopausal patients [observation period is 10 years from initiation of treatment]
overall survival [observation period is 10 years from initiation of treatment]
toxicity of letrozole + triptorelin and letrozole + zoledronic acid + triptorelin in premenopausal patients [monthly]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country
1	S. Giuseppe Moscati	Avellino	AV	Italy
2	Azienda Ospedaliera Treviglio - Caravaggio	Treviglio	BG	Italy
3	Azienda Ospedaliera G. Rummo	Benevento	BN	Italy
4	Ospedale Senatore Antonio Perrino	Brindisi	BR	Italy
5	Istituto Romagnolo per lo Studio e la Cura dei Tumori	Meldola	FC	Italy
6	Presidio Ospedaliero Di Saronno Aziendo Ospedaliera di Busto Arsizio	Saronno	VA	Italy
7	Ospedale Santa Maria Annunziata	Bagno a Ripoli		Italy
8	Istituto Nazionale per la ricerca Sul Cancro	Genova		Italy
9	Ospedale Riuniti	Livorno		Italy
10	Ospedale Unico della Versilia	Lucca		Italy
11	Istituto Nazionale dei Tumori,	Napoli		Italy
12	Ospedale Cardarelli	Napoli		Italy
13	Seconda Università di Napoli	Napoli		Italy
14	Università Federico II, Cattedra di Oncologia Medica	Napoli		Italy
15	Casa di Cura La Maddalena	Palermo		Italy
16	Ospedale Silvestrini	Perugia		Italy
17	Ospedale Santa Chiara	Pisa		Italy
18	Università di Sassari	Sassari		Italy
19	Ospedale Santa Chiara	Trento		Italy
20	ASL Viterbo Ospedale Belcolle	Viterbo		Italy

Sponsors and Collaborators

National Cancer Institute, Naples
University of Campania "Luigi Vanvitelli"

Investigators

Principal Investigator: Andrea De Matteis, M.D., NCI Naples, Division of Medical Oncology C
Principal Investigator: Ciro Gallo, M.D., Ph.D., University of Campania "Luigi Vanvitelli"
Principal Investigator: Francesco Perrone, M.D., Ph.D., NCI Naples, Clinical Trials Unit