UMIN-CTR Clinical Trial

Public title

Investigation of Dual-HER2 Blockage Therapy in HER2-Positive Breast Cancer (exploratory randomized P-II)( JBCRG-16 NeoLath)

Acronym

JBCRG-16(Neo-LaTH)

Scientific Title

Investigation of Dual-HER2 Blockage Therapy in HER2-Positive Breast Cancer (exploratory randomized P-II)( JBCRG-16 NeoLath)

Scientific Title:Acronym

JBCRG-16(Neo-LaTH)

Region

Japan

Condition

Female patients with operative HER2 positive primary breast cancer

Classification by specialty

Hematology and clinical oncology

Breast surgery

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

To investigate the efficacy and safety of dual-HER2 blockage therapy in HER2-positive breast cancer.
(1) To evaluate the efficacy and safety of trastuzumab(T) and lapatinib(L) therapy followed by combined with paclitaxel(P) in the neoadjuvant setting
(2) To verify the period of T and L dual anti-HER2 therapy based on efficacy and safety (6 weeks vs 18 weeks).
(3) To verify T and L combined with anti-endocrine therapy based on efficacy and safety in the patients with ER-p0sitive and HER2-positive charactersitics.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Phase II

Primary outcomes

pCR (including residual DCIS, breast only)

Key secondary outcomes

(1) Safety
(2) Clinical response rate (ORR)
(3) Breast conservation rate
(4) QpCR
(5) pCR (including residual DCIS, breast + axillary)
(6) SpCR

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is considered as adjustment factor in dynamic allocation.

Blocking

Concealment

Central registration

No. of arms

5

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Group A: ER-negative
Lapatinib(L)+Trastuzumab(T) 6 weeks
followed by L+T+paclitaxel (P) 12 weeks

Interventions/Control_2

Group B: ER-negative
L+T 18 weeks
followed by L+T+P 12 weeks

Interventions/Control_3

Group C: ER-positive
L+T 6 weeks
followed by L+T+P 12 weeks

Interventions/Control_4

Group D: ER-positive
L+T+anti-hormonal therapy(H) 6 weeks
followed by L+T+H+P 12weeks

Interventions/Control_5

Group E: ER-positive
L+T+H 18 weeks
followed by L+T+H+P 12weeks

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

70

years-old

>=

Gender

Female

Key inclusion criteria

1.First key inclusion criteria
(1)Age between 20 and 70 years
(2)Female patients with primary breast cancer which is diagnosed as invasive cancer by needle biopsy or tissue biopsy.
(3)Resectable primary breast cancer (T1c-3N0-1M0) with a tumor size <-7cm in diameter (multiple ipsilateral breast cancer is eligible when at least one lesion meets the eligibility criteria. However, each lesion has to be histologically evaluated).
(4)The invasive component of the primary tumor is confirmed as HER2 positive (IHC 3+ or FISH+)
(5) ER and PgR statuses are confirmed by IHC
(6) no previous therapy for breast cancer
(7) Pt has been confirned as suitable indication for primary systemic therapy
(8)The primary lesion allows imaging evaluation at baseline and after the end of study treatment using the same modality either CT scan, MRI or ultrasonography.
(9) Written informed concents

2. Secondary criteria
By the pathological central review, HER2-positive invasive ductal carcionma has been confirmed.
(1) ECOG performance status (PS) 0-1
(2) Laboratory test results meet the following criteria (within 14 days before registration)
neutrophil count: =>1,500/mm3
Hemoglobin: => 9.0g/dL
Platelet count: =>100,000/mm3
AST and ALT: <= 2.5 x upper limit of normal (ULN) established at site
ALP: <= 2.5 x ULN
Total bilirubin: <= 1.5 x ULN
Serum creatinine: <= 1.5 x ULN
(3) Baseline left ventricular ejection fraction (LVEF) => 50% measured by echocardiography or MUGA scan.
(4) No QTc prolongation by electrocardiography (ECG) (QTc: <=470 msec)
(5) No interstitial pneumonia or pulmonary fibrosis diagnosed by chest CT scan
(6) In screening for hepatitis B, determinations of HBsAg is negative
(7) If a patient's postmenopausal status cannot be confirmed, her pregnancy test must be negative (urinary or serum HCG negative) (excluding ovariectomized or hysterectomized patients)

Key exclusion criteria

(1)History or drug hypersensitivity that is relevant for the treatment in the study (i.e., past history of immediate or delayed hypersensitivity reaction to compounds chemically similar to lapatinib and its excipients)
(2)Uncontrolled concurrent disease
(3)Active infection, or pyrexia that indicates suspected infection
(4)Symptoms of varicella
(5)Pleural or pericardial effusion requiring treatment
(6)Past gastric or small bowel resection, or malabsorption or gastrointestinal dysfunction, except for ulcerative colitis
(7)Use of concomitant medication (e.g, CYP3A4 inhibitors/inducers) or non-drug therapy prohibited
(8)Current chronic use of systemic corticosteroids; in ER-positive patients, current treatment with any drug product containing estrogen or any selective estrogen receptor modulator
(9)Dementia or past history of serious psychiatric disease or current treatment for such a disease
(10)Bilateral breast cancer whether synchronous or metachronous. Patients who had lobular carcinoma in situ [LCIS] in the contralateral breast may be enrolled.
(11)Patients with multiple cancer except for adequately treated noninvasive cancer (DCIS/LCIS), nonmelanoma skin cancer, cervical cancer, thyroid cancer, early gastric cancer and early colorectal cancer. Lesions consistent with carcinoma in situ or intramucosal carcinoma that have been considered cured by local treatment are not included in multiple cancer.
(12)Prior treatment with taxane anticancer drugs
(13)Pregnant, lactating or women of childbearing potential
(14)Participation in another clinical trial
(15)Patients otherwise considered ineligible for enrollment in the study by the investigator

Target sample size

200

Name of lead principal investigator

1st name	1) Masakazu 2) Norikazu
Middle name
Last name	1) Toi 2) Masuda

Organization

1) Kyoto University Graduate School of Medicine
2) National Hospital Organization Osaka National Hospital

Division name

1)Breast Surgery, 2) Department of surgery, Breast oncology

Zip code

606-8507

Address

54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, Japan

TEL

075-751-3660

Email

neolath_office@ml.kuhp.kyoto-u.ac.jp

Name of contact person

1st name	Hiroi
Middle name
Last name	Kasai

Organization

Kyoto University Hospital

Division name

Translational Research Center

Zip code

606 8507

Address

54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto, Japan

TEL

075-751-4722

Homepage URL

https://www.jbcrg.jp/

Email

neolath_office@ml.kuhp.kyoto-u.ac.jp

Institute

Japan Breast Cancer Research Group(JBCRG)

Institute

Department

Personal name

Organization

GlaxoSmithKline K.K.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Japan

Co-sponsor

Name of secondary funder(s)

Organization

N/A

Address

N/A

Tel

N/A

Email

N/A

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

初回届出年月日：2002年9月6日　届出回数：15回

Institutions

独立行政法人国立病院機構　大阪医療センター（大阪府）
群馬県立がんセンター(群馬県)
千葉県がんセンター(千葉県)
埼玉県立がんセンター(埼玉県)
筑波大学附属病院(茨城県)
東京都立駒込病院(東京都)
地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(神奈川県)
愛知県がんセンター中央病院　乳腺科部(愛知県)
広島市立広島市民病院(広島県)
独立行政法人国立病院機構　九州がんセンター(福岡県)
独立行政法人国立病院機構　四国がんセンター(愛媛県)
国家公務員共済組合連合会 虎の門病院（東京都）
独立行政法人国立病院機構　呉医療センター・中国がんセンター（広島県）
日本大学医学部附属板橋病院（東京都）
京都大学医学部附属病院（京都府）

Date of disclosure of the study information

2012

Year

03

Month

26

Day

URL releasing protocol

Publication of results

Partially published

URL related to results and publications

Number of participants that the trial has enrolled

246

Results

Poster:14th St.Gallen Breast Cancer Conference(2015)
Symposia:The 23rd Annual Meeting of the Japanese Breast Cancer Society(2015)

Results date posted

2019

Year

09

Month

05

Day

Results Delayed

Delay expected

Results Delay Reason

Additional publication is awaiting.

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

Main results already published

Date of protocol fixation

2011

Year

12

Month

16

Day

Date of IRB

2011

Year

12

Month

16

Day

Anticipated trial start date

2012

Year

03

Month

26

Day

Last follow-up date

2013

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

03

Month

26

Day

Last modified on

2021

Year

06

Month

16

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008931