UMIN-CTR Clinical Trial

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

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

Objectives
Narrative objectives1	Phase I study to evaluate the safety of combination of convection-enhanced delivery of nimustine hydrochloride and oral temozolomide against recurrent glioma at brainstem. This study is designed to find the appropriate dose of nimustine hydrochloride.
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I

Assessment
Primary outcomes	Determination of maximum tolerable concentration of ACNU
Key secondary outcomes	Response rate, 6 months survival, Overall survival

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	First 3 cases receive convection- enhanced delivery of 7ml solution (volume is fixed to 7 ml throughout the study) of 0.25 mg/ml nimustine hydrochloride (mixed with 1mM Gd-DOTA: this concentration will be constant independent of concentration of ACNU). If no adverse event observed with this starting concentration, another 3 cases receive twice higher concentration, then 3 cases with 1.5 times higher concentration, then 3 cases with 1.2 times higher concentration. Concentration will be elevated by 1.2 times in this manner until severe adverse events will be recorded. If any severe adverse events observed within each 3 cases, another 3 cases receive the same concentration. If more than 3 in 6 cases suffer severe adverse events, this will be defined as dose-limiting toxicity. If dose-limiting toxicity was found in this method, the one step lower concentration will be defined as maximum tolerable concentration. If more than 3 cases out of 6 cases suffer severe adverse events at starting concentration, concentration will be cut to half. MRI obtained at least 14 days after initiation of CED need to be evaluated to determine the existence of adverse events.
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 standard regimen; radiation plus oral temozolomide. 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 (<1.5 mg/dl) should be cleared (within 14days of study initiation) 5) Informed consent taken from the patient. If 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) Pregnant women 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 (>1.5 mg/dl) 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	15

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

Public contact
Name of contact person	1st name Middle name Last name Ryuta Saito
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
Homepage URL
Email	ryuta@nsg.med.tohoku.ac.jp

Sponsor
Institute	Department of Neurosurgery, Tohoku University Graduate School of Medicine
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	東北大学病院　Tohoku University Hospital

Other administrative information
Date of disclosure of the study information	2011 Year 02 Month 22 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	Completed
Date of protocol fixation	2010 Year 11 Month 30 Day
Date of IRB
Anticipated trial start date	2011 Year 02 Month 01 Day
Last follow-up date	2016 Year 08 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2011 Year 02 Month 22 Day
Last modified on	2018 Year 03 Month 31 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006092

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

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