UMIN-CTR Clinical Trial

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

recurrent glioma at brainstem

Classification by specialty

Neurosurgery

Classification by malignancy

Malignancy

Genomic information

NO

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

Primary outcomes

Determination of maximum tolerable concentration of ACNU

Key secondary outcomes

Response rate, 6 months survival, Overall survival

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Department of Neurosurgery, Tohoku University Graduate School of Medicine

Institute

Department

Personal name

Organization

Tohoku University

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

東北大学病院　Tohoku University Hospital

Date of disclosure of the study information

2011

Year

02

Month

22

Day

URL releasing protocol

Publication of results

Unpublished

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

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 related information

Registered date

2011

Year

02

Month

22

Day

Last modified on

2018

Year

03

Month

31

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000006092