UMIN-CTR Clinical Trial

Basic information
Public title	Phase II trial of eribulin in patients with recurrent glioblastoma (ENIGMA)
Acronym	Phase II trial of eribulin in patients with recurrent glioblastoma
Scientific Title	Phase II trial of eribulin in patients with recurrent glioblastoma (ENIGMA)
Scientific Title:Acronym	Phase II trial of eribulin in patients with recurrent glioblastoma
Region	Japan

Condition
Condition	Glioblastoma
Classification by specialty	Neurosurgery
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
Narrative objectives1	The aim of this multicenter open-label single-arm phase II study is to evaluate the safety and efficacy of eribulin mesylate in patients with recurrent glioblastoma previously treated with temozolomide, radiation therapy and bevacizumab.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Phase II

Assessment
Primary outcomes	One-year survival rate
Key secondary outcomes	Overall survival (OS), Progression-free survival (PFS), Response rate, QOL, safety

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
Interventions/Control_1	Patients receive eribulin mesylate (1.4 mg/m2) intravenously once a week (q1w) on day 1 and day 8, and do not receive the drug on day 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
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	75 years-old >=
Gender	Male and Female
Key inclusion criteria	1) Histologically proven diagnosis of glioblastoma (including giant cell glioblastoma and gliosarcoma). 2) Evidence of progression or recurrence of glioblastoma confirmed on contrast-enhanced MRI within 14 days prior to enrollment. CT with or without contrast enhancement and MRI without contrast enhancement are not allowed. Presence of a measurable lesion is not required. 3) Corticosteroid dose must be stable or decreasing for at least 7 days prior to the contrast-enhanced MRI described in 2). 4) No episode of intracranial (including intratumoral) hemorrhage for 28 days prior to enrollment. 5) No evidence of tumors in the cerebellum, brain stem, pituitary gland, optic nerve and olfactory nerve, and no evidence of meningeal dissemination. 6) Prior treatment with postoperative temozolomide concomitantly with radiotherapy and at least for two cycles (5/28d) as an adjuvant treatment at newly-diagnosed setting. 7) History of bevacizumab treatment. 8) No history of eribulin treatment. 9) More than 180 days after initiation of temozolomide concomitant with radiation therapy have past at enrollment. 10) More than 90 days after completion of radiotherapy have past at enrollment. For patients who underwent reoperation, more than 14 days have past postoperatively at enrollment. 11) More than 28 days after completion of any other chemotherapeutic treatment including bevacizumab have past at enrollment. 12) Age between 20 and 75 years at enrollment. 13) KPS >= 70 within 14 days prior to enrolment. 14) Adequate organ and bone marrow function as defined below. All screening labs should be performed within 14 days prior to enrollment and G-CSF administration is not allowed in this period: i) absolute neutrophil count >= 1,500/mm3 ii) platelets >= 100,000/mcL iii) hemoglobin >= 9.0 g/dL iv) AST <= 100 U/L v) ALT <= 100 U/L vi) creatinine <= 1.5mg/dL 15) Written informed consent.
Key exclusion criteria	1) History of malignancy except for malignant glioma for at least 2 years prior to enrollment (those who had adequately treated carcinoma in situ, intramucosal carcinoma or equivalent malignancy can be enrolled). 2) Active infection requiring systemic therapy. 3) Body temperature >= 38 degrees Celsius at enrollment. 4) Clinical or radiographic evidence of interstitial pneumonia or pulmonary fibrosis at enrollment. 5) Positive HIV antibody, HBs antigen or HCV antibody (however, those who are positive for HCV antibody but negative for HCV-RNA detection can be enrolled). 6) Negative HBs antigen but positive HBs or HBc antibody, and positive HBV-DNA detection (those who are negative for HBV-DNA detection can be enrolled). HBV-DNA test is not necessary for those who are positive for HBs antibody only (including medical workers). 7) Women during pregnancy, possible pregnancy or breastfeeding 8) Uncontrolled diabetes mellitus. 9) Clinically significant heart dysfunction, or history of heart dysfunction. 10) Psychosis or with psychotic symptoms that disturb regular daily life and prevent trial participation. 11) Allergy or any reason to prohibit the use of contrast enhancement agent for MRI.
Target sample size	38

Research contact person
Name of lead principal investigator	1st name Yoshitaka Middle name Last name Narita
Organization	National Cancer Center Hospital
Division name	Department of Neurosurgery and Neuro-Oncology
Zip code	104-0045
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
TEL	03-3542-2511
Email	ncch1507_enigma_office@ml.res.ncc.go.jp

Public contact
Name of contact person	1st name Masamichi Middle name Last name Takahashi
Organization	National Cancer Center Hospital
Division name	Department of Neurosurgery and Neuro-Oncology
Zip code	104-0045
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
TEL	03-3542-2511
Homepage URL
Email	ncch1507_enigma_office@ml.res.ncc.go.jp

Sponsor
Institute	National Cancer Center
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)	Eisai Co., Ltd.

IRB Contact (For public release)
Organization	National Cancer Center Institutional Review Board
Address	5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
Tel	03-3542-2511
Email	NCC_IRBoffice@ml.res.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	埼玉医科大学国際医療センター（埼玉県）、国立がん研究センター中央病院（東京都）、杏林大学医学部付属病院（東京都）、東京女子医科大学病院（東京都）、東京大学医学部附属病院（東京都）、京都大学医学部附属病院（京都府）、熊本大学病院（熊本県）

Other administrative information
Date of disclosure of the study information	2017 Year 12 Month 19 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	38
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	2017 Year 09 Month 29 Day
Date of IRB	2017 Year 11 Month 28 Day
Anticipated trial start date	2018 Year 01 Month 10 Day
Last follow-up date	2021 Year 06 Month 30 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2017 Year 12 Month 12 Day
Last modified on	2021 Year 10 Month 13 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034631