UMIN-CTR Clinical Trial

Basic information
Public title	A Multicenter Phase II study of Trastuzumab emtansine for non-small cell lung cancer positive for HER2 exon 20 insertion mutation.
Acronym	PRECISION trial
Scientific Title	A Multicenter Phase II study of Trastuzumab emtansine for non-small cell lung cancer positive for HER2 exon 20 insertion mutation.
Scientific Title:Acronym	PRECISION trial
Region	Japan

Condition
Condition	Advanced non-small cell lung cancer positive for HER2 exon 20 insertion mutation
Classification by specialty	Pneumology
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy and safety in the treatment of trastuzumab emtansine (T-DM1) for advanced non-small cell lung cancer positive for HER2 exon 20 insertion mutation
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Response rate: RR
Key secondary outcomes	Progression-free survival: PFS Overall Survival: OS Duration of Response: DoR Percentage of patients with at least 1 adverse event

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	Intravenous administration of T-DM1 (3.6 mg/kg) on day1 q21 days until discontinuation of the protocol unless any of the discontinuation criteria of protocol treatment is applicable.
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	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1.Confirmed histologically or cytologically as NSCLC 2.Clinical stage III or IV or postoperative recurrent NSCLC 3.Positive for HER2 exon 20 insertion 4.Tissue samples of FFPE (5 micrometer x 10 slices) are thought to be available with consent of the patient 5.Eastern Cooperative Oncology Group (ECOG) performance status: 0 to 2 6.Treatment history of chemotherapy within 1 or 2 regimens. Single use of immune-checkpoint inhibitors or adjuvant chemotherapy which passed over 24 weeks (168 days) from the last administration are not included in the count of regimen. Combination use of immune-checkpoint inhibitors and chemotherapy is deemed as 1 regimen 7. Aged 20 years or older at the time of informed consent 8.Harboring one or more measurable disease assessed by RECIST v1.1 9.Without SVC syndrome, pericardial effusion, pleural effusion or ascites with Grade 3 or more (CTCAE v5.0) 10. LVEF >= 50% assessed by echocardiogram within 28 days 11. Sufficient time has passed from the previous treatment a) operation with general anesthesia: 2 weeks b) biopsy with incision and treatment for injury: 2 weeks c) palliative radiotherapy for metastasis: 2 weeks (gamma knife or SRS for brain metastasis: 1 week) 12. All of the following criteria are met based on the latest data obtained within 14 days before enrollment 1)Neutrophil count >= 1,500/microliter 2)Hemoglobin >= 9.0 g/dL 3)Platelet count >= 10X10^4/ microliter 4)Total bilirubin <= 1.5 x ULN 5)AST <= 2.5 x ULN 6)ALT <= 2.5 x ULN 7)Serum creatinine <= 1.5 x ULN 8)PT and APTT <= 1.5 x ULN 9) SpO2 >= 92% at room air. Patients with SpO2 < 92% are eligible if PaO2 is >= 60 torr. 10)Provided written informed consent
Key exclusion criteria	1.Patients with an infection requiring systemic treatment 2.Patients with treatment history of HER2 inhibitors 3.History of hypersensitivity of grade 3 or more to additive substance (sodium succinate, sucrose, polysorbate 20) of that of severe hypersensitivity to other drugs 4.Patients with clinically significant psychiatric disease or symptom that would interfere with participation in this study. 5.With driver mutation other than HER2 mutation (EGFR activating mutation, ALK fusion gene, ROS1 fusion gene, BRAF V600E, RET fusion gene, MET exon 14 skip mutation, NTRK fusion gene) 6.Patients with symptomatic brain metastases 7.Patients with carcinomatous meningitis 8.Patients with active double cancer 9.Patients with poorly controlled hypertension or diabetes mellitus 10.Patients with clinically meaningful heart diseases including 1)New York Heart Association(NYHA)class II or more or heart disorder with Grade 3 or more assessed by CTCAE v5.0 2)Patients with congestive heart failure or medication-needed ventricular arrythmia within 6 months 11.Patients with clinically meaningful coronary artery disease (unstable angina, myocardial infarct) within 6 months 12. Patients with positive for hepatitis B surface (HBs) antigen or positive hepatitis C virus (HCV) antibody 13. Patients with distinct interstitial pneumonitis or pulmonary fibrosis based on chest CT 14. Pregnant or lactating females. Females of child-bearing potential with the positive result of the urine pregnancy test that was carried out within 14 days before enrollment
Target sample size	20

Research contact person
Name of lead principal investigator	1st name Isamu Middle name Last name Okamoto
Organization	Kyushu University Hospital
Division name	Research Institute for Diseases of the Chest
Zip code	812-8582
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
TEL	092-642-5378
Email	okamotoi@kokyu.med.kyushu-u.ac.jp

Public contact
Name of contact person	1st name Isamu Middle name Last name Okamoto
Organization	Kyushu University Hospital
Division name	Research Institute for Diseases of the Chest
Zip code	812-8582
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
TEL	092-642-5378
Homepage URL
Email	okamotoi@kokyu.med.kyushu-u.ac.jp

Sponsor
Institute	Kyushu University Hospital
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development:AMED
Organization
Division
Category of Funding Organization	Other
Nationality of Funding Organization	Japan

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

IRB Contact (For public release)
Organization	Kyushu University Institutional Review Board
Address	3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Tel	092-642-5774
Email	ishida-e@med.kyushu-u.ac.jp

Secondary IDs
Secondary IDs	YES
Study ID_1	JapicCTI-194620
Org. issuing International ID_1	Japic Clinical Trials Information
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	九州大学病院（福岡県）　　　　　　 Kyushu University Hospital 大阪市立総合医療センター（大阪府） Osaka City General Hospital 鳥取大学医学部附属病院（鳥取県）　　　　 Tottori University Hospital 名古屋大学医学部附属病院（愛知県）　　　 Nagoya University Hospital がん研究会有明病院（東京都）　　　　　　 Cancer Institute Hospital 仙台厚生病院（宮城県） Sendai Kousei Hospital 国立がん研究センター 東病院（千葉県）　　National Cancer Center Hospital East 静岡県立静岡がんセンター（静岡県）　　　 Shizuoka Cancer Center

Other administrative information
Date of disclosure of the study information	2019 Year 01 Month 22 Day

Related information
URL releasing protocol
Publication of results	Published

Result
URL related to results and publications
Number of participants that the trial has enrolled	22
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results	2021 Year 12 Month 24 Day
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	2018 Year 11 Month 27 Day
Date of IRB	2019 Year 01 Month 07 Day
Anticipated trial start date	2019 Year 02 Month 01 Day
Last follow-up date	2021 Year 03 Month 31 Day
Date of closure to data entry	2021 Year 05 Month 24 Day
Date trial data considered complete	2021 Year 06 Month 03 Day
Date analysis concluded	2021 Year 06 Month 17 Day

Other
Other related information

Management information
Registered date	2019 Year 01 Month 22 Day
Last modified on	2022 Year 01 Month 24 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000040516