UMIN-CTR Clinical Trial

Basic information
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
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

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	Japan Breast Cancer Research Group(JBCRG)
Institute
Department

Funding Source
Organization	GlaxoSmithKline K.K.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	N/A
Address	N/A
Tel	N/A
Email	N/A

Secondary IDs
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
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）

Other administrative information
Date of disclosure of the study information	2012 Year 03 Month 26 Day

Related information
URL releasing protocol
Publication of results	Partially published

Result
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

Progress
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
Other related information

Management information
Registered date	2012 Year 03 Month 26 Day
Last modified on	2021 Year 06 Month 16 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008931