UMIN-CTR Clinical Trial

Basic information
Public title	Phase II study of neoadjuvant treatment with Exemestane for 24 weeks in postmenopausal women with hormone receptor positive Stage II or IIIA breast cancer.
Acronym	Neoadjuvant Exemestane for 24 weeks in postmenopausal Women with hormone receptor positive Stage II or IIIA breast cancer (JFMC34-0601)
Scientific Title	Phase II study of neoadjuvant treatment with Exemestane for 24 weeks in postmenopausal women with hormone receptor positive Stage II or IIIA breast cancer.
Scientific Title:Acronym	Neoadjuvant Exemestane for 24 weeks in postmenopausal Women with hormone receptor positive Stage II or IIIA breast cancer (JFMC34-0601)
Region	Japan

Condition
Condition	Breast Cancer
Classification by specialty	Hematology and clinical oncology Breast surgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Examine the clinical response and safety of neoadjuvant therapy with Exemestane for 24 weeks in postmenopausal women with hormone receptor positive Stage II or IIIA breast cancer. As secondary object, develop a predictive model of response and long term outcomes based on gene expression and proteomics profiling.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase II

Assessment
Primary outcomes	Determine the clinical response rate. Determine the incidence of adverse events.
Key secondary outcomes	Determine the long-term outcomes (overall survival, relapse free survival). Determine the rate of improvement in surgical outcomes (breast conserving rate, local recurrence rate). Determine the rate of axillary lymph node involvement and pathologic response. Examine the change of biomarker (e.g., Ki-67, TUNEL, bcl-2, M-30) with this treatment. Develop a predictive model of response and long term outcomes based on gene expression and proteomics profiling.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Preoperative treatment with Exemestane 25mg/day for 24 weeks.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	55 years-old <=
Age-upper limit	79 years-old >=
Gender	Female
Key inclusion criteria	1) Histologically confirmed invasive breast cancer excluding mucinous and lobular cancer by core needle biopsy or open biopsy. 2) Clinical stage T2-T3, N0-2, M0. 3) Estrogen- and/or Progesterone-receptor positive tumor based on 10% or more nuclear staining of the invasive ductal component by immunohistochemistry. 4) Her2 expression was examined by IHC and/or FISH. 5) Previously untreated disease. 6) WHO performance status 0-1. 7) Expecting benefits from neoadjuvant therapy that would improve surgical outcome and meets criteria for 1 of the following: (a) Marginal candidate for lumpectomy (e.g., lumpectomy feasible but patient at risk for positive margins or poor cosmetic outcome). (b) Ineligible for lumpectomy, but modified radical mastectomy feasible. 8) Sentinel lymph node biopsy allowed before treatment or after treatment. 9) Patients must be age between 55 y.o. to 79 y.o. and postmenopausal verified by one of the following. (a) amenorrhea more than 1 year (b) artificial menopause by radiation or bilateral ovariectomy (c) FSH >= 30mIU/ml and E2 < 10pg/ml 10) Willing and able to provide biopsy materials and blood samples for research purpose. 11) No severe liver dysfunction. 12) Confirmed by attending doctor as a candidate for this trial after consideration of other treatment options. 13) Written informed consent
Key exclusion criteria	1) Concurrent user of HRT, raloxifen and other sex hormone related drugs. 2) Patients with bilateral breast cancer, past history of breast cancer and active other type of cancer. 3) Absolute candidate for primary chemotherapy or surgery.
Target sample size	110

Research contact person
Name of lead principal investigator	1st name Middle name Last name Masakazu Toi
Organization	Graduate School of Medicine, Kyoto University
Division name	Department of Surgery (Breast Surgery)
Zip code
Address	54 Shogoin-Kawaramachi, Sakyo-ku, Kyoto 606-8507, Japan
TEL	075-751-3660
Email	toi@kuhp.kyoto-u.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Japanese Foundation for Multidisciplinary Treatment of Cancer
Organization	Japanese Foundation for Multidisciplinary Treatment of Cancer
Division name	Office
Zip code
Address	TaniBuilding3F, 1-28-6, kameido, koutou-ku, Tokyo, 136-0071, Japan
TEL	03-5627-7594
Homepage URL	http://www.jfmc.or.jp/
Email	jfmc-dc@jfmc.or.jp

Sponsor
Institute	Japanese Foundation for Multidisciplinary Treatment of Cancer
Institute
Department

Funding Source
Organization	Japanese Foundation for Multidisciplinary Treatment of Cancer
Organization
Division
Category of Funding Organization	Non profit foundation
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions

Institutions

札幌医科大学 第一外科（北海道）、岩手医科大学 外科（岩手）、福島県立医科大学 第二外科（福島）、筑波大学 乳腺甲状腺内分泌外科（茨城）、群馬県立がんセンター 乳腺科（群馬）、埼玉医科大学国際医療センター 乳腺腫瘍科（埼玉）、埼玉県立がんセンター 乳腺外科（埼玉）、東京都立駒込病院 外科（東京）、順天堂大学医学部附属練馬病院 乳腺外科（東京）、昭和大学病院 一般･消化器外科（東京）、東邦大学医療センター大森病院 乳腺･内分泌外科（東京）、東京医科大学 乳腺科（東京）、国立国際医療センター 外科（東京）、東京女子医科大学 東医療センター 外科（東京）、癌研究会有明病院 化学療法科（東京）、日本大学医学部附属板橋病院 乳腺内分泌外科（東京）、東京都立府中病院 外科（東京）、三井記念病院 乳腺内分泌外科（東京）、聖路加国際病院 乳腺外科（東京）、国際医療福祉大学三田病院 乳腺センター （東京）、神奈川県立がんセンター 乳腺甲状腺外科（神奈川）、東海大学医学部 乳腺内分泌外科（神奈川）、信州大学医学部附属病院 乳腺内分泌外科（長野）、新潟県立がんセンター新潟病院 外科（新潟）、藤田保健衛生大学病院 乳腺外科（愛知）、愛知県がんセンター中央病院 乳腺科（愛知）、名古屋市立大学病院 乳腺内分泌外科（愛知）、京都大学 乳腺外科（京都）、国立病院機構大阪医療センター 外科（大阪）、関西労災病院 外科（大阪）、広島市立安佐市民病院 外科（広島）、国立病院機構四国がんセンター 乳腺科（愛媛）、北九州市立医療センター 外科（福岡）、国立病院機構九州がんセンター 乳腺科（福岡）、医療法人にゅうわ会及川病院 外科･乳腺腫瘍科（福岡）、熊本大学医学部附属病院 乳腺･内分泌外科（熊本）、熊本市立熊本市民病院 乳腺内分泌外科（熊本）

Other administrative information
Date of disclosure of the study information	2006 Year 03 Month 06 Day

Related information
URL releasing protocol	http://www.jfmc.or.jp/wp-content/uploads/2015/01/jfmc34-0601_070117.pdf
Publication of results	Partially published

Result
URL related to results and publications	https://doi.org/10.1111/j.1349-7006.2011.01867.x
Number of participants that the trial has enrolled	116
Results	Between March 2006 and December 2007, 116 patients were enrolled. Among those, 102 patients completed 24 weeks administration. The ORR was 47% (55/116) at week 16 and 51% (59/116) at week 24, respectively. No serious toxicity was seen. At diagnosis, 59 patients (51%) would have required mastectomy but 40 patients were converted to BCS, showing an increase in the rate of BCS (77%). The 24-week aromatase inhibition provided preferable clinical benefits with significant reduction in Ki67 index.
Results date posted	2019 Year 03 Month 18 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Between March 2006 and December 2007 a total of 116 patients were enrolled. T2 stage were 110 cases and N0 were 91 cases. All patients were defined as ER-positive, 80 (68.9%) were PgR-positive and 3(2.5%) were HER2-positive by investigator evaluation.
Participant flow	During the first 16 weeks, 10 patients discontinued neoadjuvant exemestane treatment because of PD (4 patients), investigator decision (1 patient), adverse events (2 patients, 1 of whom was not evaluable at Week 16), or patients decision (3 patients, 2 of whom were not evaluable at Week 16). 102 patients completed 24 weeks of exemestane neoadjuvant treatment.
Adverse events	The most frequently seen adverse events were an abnormal increase in liver enzyme levels (SGOT, SGPT and ALP), hot flush, joint pain, hypoalbuminuria and elevated creatinine and bilirubin levels. None of these adverse events were deemed to be severe in intensity. The only Grade 3 adverse events were elevated liver enzymes in four cases.
Outcome measures	The primary end points were objective response rates (ORR) and safety after 16 and 24 weeks of treatment in intent to treatment analysis.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2006 Year 02 Month 06 Day
Date of IRB	2005 Year 11 Month 25 Day
Anticipated trial start date	2006 Year 03 Month 01 Day
Last follow-up date	2018 Year 08 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2006 Year 03 Month 02 Day
Last modified on	2019 Year 03 Month 18 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000000443

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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