UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Convection-enhanced delivery of Nimustine Hydrochloride combined with oral Temozolomide after surgical resection of recurrent malignant gliomas at first recurrence / Phase I/II study
Title of the study (Brief title)	ACNU/CED plus oral TMZ after surgical resection of recurrent malignant gliomas at first recurrence
Region	Japan

Condition
Condition	malignant glioma
Classification by specialty	Neurosurgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	Phase I/II study to evaluate the safety and efficacy of combination of convection-enhanced delivery of nimustine hydrochloride and oral temozolomide after surgical resection of recurrent glioma at first recurrence.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2	Pragmatic
Developmental phase	Phase I,II

Assessment
Primary outcomes	Phase I: Determination of maximum tolerable concentration of ACNU Phase II: 6 months progression free survival rate
Key secondary outcomes	Progression free 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 20ml solution (volume is fixed to 20 ml throughout the study) of 0.25 mg/ml nimustine hydrochloride (mixed with 5mM 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 (DLT). If dose-limiting toxicity was found in this method, the one step lower concentration will be defined as maximum tolerable concentration. If more than 2 cases out of 6 cases suffer severe adverse events at starting concentration, concentration will be cut to half. Concentration one-step lower than DLT will be defined as Maximum tolerable concentration (MTC). After determination of MTC, Phase II study using MTC will evaluate the efficacy of this treatment recruiting about 10 patients.
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) First recurred operable malignant glioma cases in patients who already received initial treatment with histological diagnosis of malignant glioma . 2) Recurrent cases after treatment with standard regimen; radiation plus oral temozolomide for grade IV or radiation plus intravenous ACNU for grade III. 3) Histological diagnosis of recurrent tumor from surgery performed within two weeks from initiation of CED of ACNU. 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. 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) Severe liver dysfunction (GOT>100 IU/l or GPT>100 IU/l) 5) Existence of bone marrow insufficiency: WBC(<2,000/mm3), Hb (<8.0 g/dl), Plt(<10x104/mm3) 6) Renal dysfunction: Cre (>1.5 mg/dl) 7) Existence of hemorrhagic diathesis 8) Patients taking anti-coagulants or anti-platelet agents. 9) Existence of mental disorder that makes participation to this study difficult. 10) Poor control of diabetes mellitus 11) Past history of acute myocardial infarction within 3 months or unstable angina. 12) Past history of pulmonary fibrosis or interstitial pneumoniae.
Target sample size	20

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

Public contact
Name of contact person	Ryuta Saito
Organization	Tohoku University Graduate School of Medicine
Division name	Department of Neurosurgery
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	Other
Nationality of Funding Organization

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

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（宮城県）

Other administrative information
Date of disclosure of the study information	2013 Year 08 Month 20 Day

Progress
Recruitment status	Completed
Date of protocol fixation	2012 Year 09 Month 25 Day
Anticipated trial start date	2013 Year 08 Month 20 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2013 Year 08 Month 20 Day
Last modified on	2018 Year 12 Month 14 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013493