UMIN-CTR Clinical Trial

Public title

Assessment of the efficacy of the use of zoledronic acid in the prevention of aromatase inhibitor-associated bone loss in postmenopausal women with hormone receptor-positive breast cancer who received letrozole as adjuvant therapy

Acronym

Z-FAST Study_Japan

Scientific Title

Assessment of the efficacy of the use of zoledronic acid in the prevention of aromatase inhibitor-associated bone loss in postmenopausal women with hormone receptor-positive breast cancer who received letrozole as adjuvant therapy

Scientific Title:Acronym

Z-FAST Study_Japan

Region

Japan

Condition

Postmenopausal Breast Cancer

Classification by specialty

Breast surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To evaluate the use of zoledronic acid in the prevention of aromatase inhibitor-associated bone loss in postmenopausal women with stage 1-3a hormone receptor-positive breast cancer who received letrozole as adjuvant therapy

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

To compare the percent change in the lumbar spine(L1-L4)BMD, as measured by DXA, at 12 months in postmenopausal women with hormone receptor-positive breast cancer randomized to zoledronic acid upfront versus delayed start.

Key secondary outcomes

1)To compare the percent change in lumbar spine(L1-L4)BMD at two years, three years, four years and five years between the two treatment groups. 2)To compare the percent change in total hip BMD at 12 months, two years, three years, four years and five years between the two treatment groups. 3)To identify changes in serum markers of bone turnover, serum NTX and BSAP, at 12 months, two years, three years, four years and five years. 4)To compare the incidence rate of all clinical fractures at three years between the two treatment groups. 5)To compare the profile of serum lipids. 6)To compare the time to disease progression between the two treatment groups. 7)To compare the overall survival between the two treatment groups. 8)Adverse events

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Blinding

Open -no one is blinded

Control

No treatment

Stratification

NO

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

All patients receive letrozole 2.5 mg orally daily for 5 years or until disease progression.

Interventions/Control_2

Patients receive zoledronic acid 4mg or an adjusted dose based on renal function IV over 15 minutes infusion every 6 months for 5 years. The Upfront group receives zoledronic acid after random assignment, whereas the delayed group receives zoledronic acid when either postbaseline lumber spine BMD decreases to YAM -2.0 SD or clinical fracture occurred.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

Not applicable

Age-upper limit

Not applicable

Gender

Female

Key inclusion criteria

1)Adequately diagnosed and treated invasive breast cancer defined as: 1.Clinical stage I,II or IIIA 2.Patients with breast cancer whose tumor were removed by an appropriate surgical procedure such as mastectomy or breast conserving surgery 2) ER and/or PgR positive defined with immunohistochemical staining 3)Postmenopausal status defined by one of the following: 1.women >54 years with cessation of menses 2.spontaneous cessation of menses within the past 1 years, but amenorrheic in women <55 years, and according to the definition of 'postmenopausal range' for FSH and estradiol level 3.bilateral oophorectomy 4)Patients with a baseline lumbar spine BMD of YAM -2.0SD or more 5)Patients who have no lumbar spine and total hip fracture 6)ECOG Performance status of 0 to 2 7)Adequate organ function 8)The date of randomization must be within 12 weeks from completion of surgery or from completion of adjuvant chemotherapy. (Completion of chemotherapy is defined as completion of the last full course including recovery time) 9)Patients who have discontinued the following drugs known as affect to the skeleton more than 4 weeks: oral bisphosphonates, estrogen, raloxifene, calcitonin, vitamin K, activated vitamin D, ipriflavone 10)A written informed consent is obtained

Key exclusion criteria

1)Patients with any clinical or radiological evidence of distant spread of their disease at any point before randomization 2)Patients with invasive bilateral breast cancer 3)Patients who have started adjuvant endocrine therapy 4)Patients who have received any endocrine therapy within the past 12 months 5)Patients who have received prior treatment with intravenous bisphosphonates within the past 12 months 6)Patients with the following diseases which may interfere with DXA scan: severe scoliosis, immobility, hyperosteosis or sclerotic changes at the lumbar spine, calcification of abdominal aorta, vertebral diseases 7)Patients with previous or concomitant malignancy (not breast cancer) within the past 5 years 8)Current active dental problems including infection of the teeth or jawbone. Recent (within 6 weeks) or planned dental or jaw surgery(e.g., extraction, implants) 9)Other conditions judged as inappropriate for the study by the investigator

Target sample size

180

Name of lead principal investigator

1st name
Middle name
Last name	Shinzaburo Noguchi

Organization

Graduate School of Medicine,
Osaka University

Division name

Department of Breast and Endocrine Surgery

Zip code

Address

2-2-E10 Yamada-oka, Suita-city, Osaka 565-0871, Japan

TEL

06-6879-5111

Email

Name of contact person

1st name
Middle name
Last name	Shunji Takahashi

Organization

Cancer Institute Hospital

Division name

Division of Medical Oncology

Zip code

Address

3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan

TEL

03-3570-0488

Homepage URL

Email

stakahas@jfcr.or.jp

Institute

Cancer Institute Hospital

Institute

Department

Personal name

Organization

None

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

None

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2008

Year

03

Month

29

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=102&abstractID=77433

Number of participants that the trial has enrolled

Results

The upfront and delayed groups included 94 and 95 patients, respectively. At 12M, L1-L4, L2-L4, TH BMD significantly decreased by 2.0%, 2.4%, 2.4%, respectively, in the delayed group. L1-L4 BMD was 4.9% higher in the upfront group than in the delayed group (95% CI, 3.9-5.8%; p<0.001). L2-L4 BMD was 5.6% higher (95% CI, 4.5-6.6%; p< 0.001), and TH BMD was 4.4% higher (95% CI, 3.3-5.4%; p<0.001). In the upfront group, mean serum N-telopeptide and bone-specific alkaline phosphatase concentrations decreased by 23.6% (p< 0.001) and 39.4% (p<0.001), respectively, at 12M, whereas concentrations tended to increase in the delayed group by 9.4% (p=0.26) and 10.2% (p= 0.46), respectively. In conclusion, at 12M, upfront ZA therapy prevented bone loss in postmenopausal Japanese women who were receiving adjuvant LET, confirming the Z-/ZO-FAST study results in Western countries.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2008

Year

01

Month

25

Day

Date of IRB

Anticipated trial start date

2008

Year

03

Month

01

Day

Last follow-up date

2014

Year

12

Month

01

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2008

Year

03

Month

28

Day

Last modified on

2011

Year

09

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001335