UMIN-CTR Clinical Trial

Basic information
Public title	A phase II, multicenter, single-arm study of Induction therapy with LDK378 followed by surgery in patients with ALK fusion-positive Stage II/III non-small cell lung cancer.
Acronym	SAKULA trial
Scientific Title	A phase II, multicenter, single-arm study of Induction therapy with LDK378 followed by surgery in patients with ALK fusion-positive Stage II/III non-small cell lung cancer.
Scientific Title:Acronym	SAKULA trial
Region	Japan

Condition
Condition	Non-small cell lung cancer
Classification by specialty	Pneumology Chest surgery
Classification by malignancy	Malignancy
Genomic information	YES

Objectives
Narrative objectives1	To evaluate the efficacy and safety of preoperative therapy with LDK378 in patients with ALK fusion gene-positive stage II/III non-small cell lung cancer (NSCLC).
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Major pathological response rate
Key secondary outcomes	･Incidence of adverse events ･Relapse-free survival: RFS ･Overall survival: OS ･Response rate: RR ･Pathological complete response rate: pCR rate ･Operability ･Complete resection rate

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 Maneuver
Interventions/Control_1	A treatment cycle is defined as 28 days from the start of LDK378. 750 mg of LDK378 is orally administered once daily. After preoperative induction treatment with LDK378 for 3 cycles, surgical resection is performed. For postoperative adjuvant treatment, LDK378 is orally administrated for 13 cycles (1 year).
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)Histologically or cytologically confirmed diagnosis of NSCLC. 2)ALK fusion gene is determined to be positive by at least 2 of the following methods: FISH, immunohistochemical (IHC) examination, and RT-PCR . 3)Clinical stage is II or III 4)It is considered that complete tumor removal can be achieved by pneumonectomy (lobectomy or more extensive surgical resection) and by lymph node dissection. 5)Predicted residual FEV1 after resection is >= 800 ml. 6)No previous treatment. 7) Male or female aged 20 years and over. 8)Performance status (ECOG) is 0 or 1. 9) At least one measurable lesion as defined by RECIST (Response Evaluation Criteria in Solid Tumor) ver1.1. 10)The following laboratory values indicative of adequate organ functions are available within 7 days before registration: a. Neutrophil count >= 1,500/mm3 b. Platelet count >= 100,000/mm3 c. Hemoglobin (Hgb) >= 10.0 g/dL d. Serum albumin >= 3.0 g/dL e. Creatinine clearance >= 30 mL/min f. Total bilirubin <= 1.5 mg/dL (total bilirubin <= 3.0 mg/dL in patients with Gilbert's syndrome) g. AST (SGOT) <= 100 IU/L h. ALT (SGPT) <= 100 IU/L i. ALP <= 1800 IU/L j. Amylase <= 300 U/L k. Lipase <= 57U/L l. Fasting plasma glucose <= 175 mg/dL ( <= 9.8 nmol/L) m. Potassium <= 5.0 mEq/L n. Magnesium <= 10.0 mg/dL o. Phosphorus <= 4.5 mg/dL p. Calcium <= 10.0 mg/dL q. SpO2 >= 93% 11)Women of child-bearing-potential show a negative result of pregnancy test conducted within 7 days before registration. Both male and female patients agree to use an appropriate method of contraception during the study and for 3 months after discontinuation of the study drug. 12)Patients expected to survive for at least 3 months after the first day of preoperative chemotherapy. 13)Patients intended and able to comply with scheduled study visit, treatment plan, laboratory tests, and other study-related procedures.
Key exclusion criteria	1) Patient with lymph node metastasis in the neck/ lymph node metastasis in the supraclavicular/ contralateral hilus and contralateral mediastinum. 2) Patient having previously experienced hypersensitivity to any additive of LDK378. 3) Patient with a history of or currently having malignant tumors other than NSCLC. 4) Patient with a history of interstitial lung disease or interstitial pneumonia. 5) Patient with any of the following clinically significant and poorly controlled heart diseases: -Unstable angina pectoris and Myocardial infarction within 6 months before registration -A history of congestive heart failure -Poorly controlled hypertension defined as systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg -Arrhythmia not controlled with drugs -QT interval > 470 msec on ECG 6) Patient with poorly controlled diabetes mellitus. 7) Patient receiving any of the following drugs and in whom it is impossible to discontinue them for at least 1 week before the start of treatment with LDK378: -Potent CYP3A4/5 inhibitor or inducer -Drugs with a small therapeutic index that are mainly metabolized by CYP3A4/5, CYP2C8 or CYP2C9 -Drugs known to prolong QT interval or induce Torsades de pointes 8) Patient receiving warfarin sodium or other coumarin anticoagulants. 9) Patient treated with corticosteroids at unstable doses. 10) Patient receiving enzyme-inducing anticonvulsants and in whom it is impossible to discontinue them for at least 1 week before the first administration of LDK378. 11) Pregnant women or breast-feeding women. 12) Patients with any major acute or chronic medical or mental condition or laboratory abnormality that is considered to increase the risk associated with participation in the study by the investigator. 14) Functional gastrointestinal tract disorder/ gastrointestinal disease that significantly prevents absorption of LDK378. 15) Patient has a history of pancreatitis/ increased amylase or lipase that was due to pancreatic disease.
Target sample size	19

Research contact person
Name of lead principal investigator	1st name Koichi Middle name Last name Goto
Organization	National Cancer Center Hospital East
Division name	Divisions of Thoracic Oncology
Zip code	2778577
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba
TEL	04-7133-1111
Email	sakula_core@east.ncc.go.jp

Public contact
Name of contact person	1st name Kiyotaka ,Yoshitaka Middle name Last name Yoh, Zenke
Organization	National Cancer Center Hospital East
Division name	Divisions of Thoracic Oncology
Zip code	2778577
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba
TEL	04-7133-1111
Homepage URL
Email	sakula_core@east.ncc.go.jp

Sponsor
Institute	National Cancer Center HospitalEast
Institute
Department

Funding Source
Organization	Japan Agency for Medical Research and Development
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

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

IRB Contact (For public release)
Organization	IRB of National Cancer Center Hospital
Address	6-5-1, Kashiwanoha, Kashiwa, Chiba
Tel	04-7133-1111
Email	irboffice@east.ncc.go.jp

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	国立がん研究センター東病院（千葉県） 北海道大学病院（北海道） 大阪市立総合医療センター（大阪府） 四国がんセンター（愛媛県） 九州大学病院（福岡県） 東京都立駒込病院（東京都）

Other administrative information
Date of disclosure of the study information	2015 Year 07 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled	7
Results
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

Progress
Recruitment status	Terminated
Date of protocol fixation	2015 Year 02 Month 10 Day
Date of IRB	2015 Year 03 Month 11 Day
Anticipated trial start date	2015 Year 07 Month 27 Day
Last follow-up date	2019 Year 08 Month 02 Day
Date of closure to data entry	2019 Year 08 Month 30 Day
Date trial data considered complete	2019 Year 09 Month 30 Day
Date analysis concluded	2019 Year 11 Month 30 Day

Other
Other related information

Management information
Registered date	2015 Year 06 Month 15 Day
Last modified on	2019 Year 12 Month 17 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000020743