UMIN-CTR Clinical Trial

Basic information
Public title	Phase II study of Convection-enhanced delivery of Nimustine Hydrochloride combined with systemic Temozolomide against recurrent gliomas at brainstem
Acronym	ACNU/CED plus systemic TMZ against recurrent gliomas at brainstem: Phase II study
Scientific Title	Phase II study of Convection-enhanced delivery of Nimustine Hydrochloride combined with systemic Temozolomide against recurrent gliomas at brainstem
Scientific Title:Acronym	ACNU/CED plus systemic TMZ against recurrent gliomas at brainstem: Phase II study
Region	Japan

Condition
Condition	recurrent glioma at brainstem
Classification by specialty	Neurosurgery Adult
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Phase II study to evaluate the efficacy of combination of convection-enhanced delivery of nimustine hydrochloride and systemic temozolomide against recurrent glioma at brainstem.
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	Determination of 3.5 months survival rate for pediatric cases and 6 months survival for adult cases
Key secondary outcomes	Overall survival, Response rate, and Adverse events

Base
Study type	Interventional

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

Intervention
No. of arms	1
Purpose of intervention	Treatment
Type of intervention	Medicine Device,equipment Maneuver
Interventions/Control_1	On Day 1, catheter will be inserted into the targeted site with the method of stereotactic neurosurgery. After the MR imaging, infusion of the drug; Nimustine hydrochloride, will be started. 7 ml Nimustine hydrochloride at concentration of 0.75 mg/ml, which is a predefined maximum tolerable concentration from preceding Phase I study, will be used in this study. In order to monitor drug distribution during infusion, 5mM Gd-DOTA will be mixed into the infusion solution. In addition, patients will receive temozolomide chemotherapy from Day 1-5. Protocol for temozolomide will be that for recurrent glioma; 200mg/m2 daily for 5 days.
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	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1) Cases diagnosed clinically as well as radiologically as recurrent glioma at brainstem will be recruited. Recurrent cases of diffuse brainstem glioma as well as recurrent cases of gliomas originating from surrounding structure, i.e. thalamus, cerebellum, etc, and infiltrating brainstem will be included. In the recurrent cases of glioma originating from surrounding structure, histological diagnosis of the initial tumor is necessary. Since the disease occupy brainstem region, histological diagnosis of brainstem lesion is not necessary. 2) Recurrent cases after treatment with radiation therapy. 3) At least 4 weeks interval from prior radiation and/or chemotherapy. 4) Appropriate systemic condition: WBC (>3,000/mm3), Hb (>8.0 g/dl), Plt (>10x104/mm3), GOT (<100 IU/l), GPT (<100 IU/l), Cre (adult<1.5 mg/dl, pediatric<2 x upper limitation of corresponding age and sex) should be cleared 5) Informed consent taken from the patient. In case it is difficult to get the signature of patient due to neurological deficits, representative person may sign as long as patient is able to understand and give his approval.
Key exclusion criteria	1) Co-existence of uncured cancer. 2) Co-existence of meningitis or pneumonia that require treatment. 3) Women in pregnancy or possibly pregnant women or breast feeding women 4) Existence of active inflammation (CRP>2.0) 5) Severe liver dysfunction (GOT>100 IU/l or GPT>100 IU/l) 6) Existence of bone marrow insufficiency: WBC(<3,000/mm3), Hb (<8.0 g/dl), Plt(<10x104/mm3) 7) Renal dysfunction: Cre (adult >1.5 mg/dl, pediatric > 2 x upper limitation of corresponding age and sex) 8) Existence of hemorrhagic diathesis 9) Patients taking anti-coagulants or anti-platelet agents. 10) Existence of mental disorder that makes participation to this study difficult. 11) Poor control of diabetes mellitus 12) Past history of acute myocardial infarction within 3 months or unstable angina. 13) Past history of pulmonary fibrosis or interstitial pneumoniae.
Target sample size	35

Research contact person
Name of lead principal investigator	1st name Middle name Last name Teiji Tominaga
Organization	Tohoku University Graduate School of Medicine
Division name	Department of Neurosurgery
Zip code
Address	1-1 Seiryo-cho, Aoba-ku, Sendai
TEL	022-717-7230
Email	tomi@nsg.med.tohoku.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Ryuta Saito
Organization	Tohoku University Hospital
Division name	Department of Neurosurgery
Zip code
Address	1-1 Seiryo-cho, Aoba-ku, Sendai
TEL	022-717-7230
Homepage URL
Email	ryuta@nsg.med.tohoku.ac.jp

Sponsor
Institute	Tohoku University
Institute
Department

Funding Source
Organization	Tohoku University
Organization
Division
Category of Funding Organization	Self funding
Nationality of Funding Organization

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

Other administrative information
Date of disclosure of the study information	2016 Year 11 Month 30 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
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	No longer recruiting
Date of protocol fixation	2016 Year 11 Month 25 Day
Date of IRB	2019 Year 01 Month 30 Day
Anticipated trial start date	2016 Year 12 Month 01 Day
Last follow-up date	2023 Year 03 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2016 Year 11 Month 29 Day
Last modified on	2021 Year 07 Month 29 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000028810