UMIN-CTR Clinical Trial

Public title

Efficacy and safety of ONO-4538 for chemo-refractory germ cell tumors: an open-label, multicentre, phase 2 trial

Acronym

Nivolumab for Chemo-refractory germ cell tumors. (NICHE-GCT study )

Scientific Title

Efficacy and safety of ONO-4538 for chemo-refractory germ cell tumors: an open-label, multicentre, phase 2 trial

Scientific Title:Acronym

Nivolumab for Chemo-refractory germ cell tumors. (NICHE-GCT study )

Region

Japan

Condition

Unresectable advanced germ cell tumors refractory to second-line or further chemotherapy

Classification by specialty

Hematology and clinical oncology

Urology

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To test the response rate of ONO-4538 for advanced germ cell tumors, failed to achieve complete response after chemotherapy and surgery by multicentre, single arm study

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Phase II

Primary outcomes

Objective response rate, central review

Key secondary outcomes

1.Objective response rate, assessment by the attending investigator's
2.Disease control rate, DCR
3.Immune-related Disease Control Rate, irDCR
4.Overall Survival, OS
5.Progression Free Survival, PFS
6.Immune-related Progression Free Survival, irPFS
7.Time to Progression,TTP
8.Duration of response
9.Time to response
10.Best overall response, BOR
11.Immune-related best overall response
12.Percent change from baseline in the diameters
13.Evaluation of response according to Japanese Classification of testicular tumor
14.Rate of metastasectomy

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

Interventions/Control_1

ONO-4538 240mg will be administered intravenously at 2-weeks intervals. Six weeks will counts as 1cycle of treatment.

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

18

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1.Patients diagnosed as gonadal or extragonadal germ cell tumor by histological examination or tumor marker profile
2.Patients received platinum based chemotherapy
3.Patients received chemotherapy using 2 or more regimens
4.Patients with no indication of curative surgery
5.Patients having chemo-refractory disease to the last chemotherapy defined by at least one of the following criteria
a)>20% increase of total diameter of target lesions by RECIST guideline v1.1
b)Development of new lesion
c)At least 2 consecutive tumor marker elevation with 1 or more weeks interval
6.Patietns with a life expectancy of at least 12 weeks
7.Patients having measurable target lesion (RECIST guideline v1.1) defined by radiological imaging study within 4 weeks prior to entry
8.ECOG performance status score 0 or 1
9.Patients whose latest laboratory data meet the below criteria within 7 days before registration.
a)Neutrophils >1,000/uL
b)Platelets >100x103uL
c)Hemoglobin>8.0g/dL
d)AST and ALT <3.0-fold the upper limit of normal(ULN)
e)Total bilirubin <2.0-fold the ULN
f)Creatinine <1.5-fold the ULN or creatinine clearance >30mL/min
10.Men must agree to use contraception from the start of study treatment until 7months or more after the last dose of the investigational product.
11.Women of childbearing potential must agree to use contraception from the time of informed consent until 5 months or more after the last dose of the investigationa1 product. Also, women must agree not to breastfeed from the time of informed consent until 5 months or more after the last dose of the investigational product.

Key exclusion criteria

1.Patients with multiple primary cancers
2.Patients with residual adverse effects of prior therapy or effects of surgery that would affect the safety evaluation of the investigational product
3.Patients with current or past history of severe hypersensitivity to any other antibody products
4.Patients with concurrent autoimmune disease or history of chronic or recurrent autoimmune disease
5.Patients with a current or past history of interstitial lung disease or pulmonary fibrosis
6.Patients with concurrent diverticulitis or symptomatic gastrointestinal ulcerative disease
7. Patients with any metastasis in the brain or meninx that is symptomatic or requires treatment.
8.Patients with intracranial germ cell tumor
9.Patients with pericardial fluid, pleural effusion, or ascites requiring treatment
10.Patients with uncontrollable, tumor-related pain
11.Ptients who have experienced a transient ischemic attack, cerebrovascular accident thrombosis, or thromboembolismwithin 180 days before registration
12. Patients with a history of uncontrollable or significant cardiovascular disease
13. Patients with uncontrollable diabetes mellitus
14.Patients with systemic infections requiring treatment
15.Patients who have received systemic corticosteroids or immunosuppressants
16.Patients who have received antineoplastic drugs
17.Patients who have undergone surgical adhesion of the pleura or pericardium
18.Patients who have undergone surgery under general anesthesia
19.Patiebts who have undergone surgery involving local or topical anesthesia
20.Patients who have received radiotherapy
21.Patients who have received any radiopharmaceuticals
22. Patients who have previously shown AIDS symptoms or with positive test results for any of the following: HIV, HTLV-1 antibody, HBs antigen, or HCV antibody

Target sample size

16

Name of lead principal investigator

1st name	Hiroyuki
Middle name
Last name	Nishiyama

Organization

University of Tsukuba Hospital

Division name

Dept. of Urology

Zip code

305-8576

Address

2-1-1 Amakubo, Tsukuba, Ibaraki

TEL

029-853-3196

Email

nishiuro@md.tsukuba.ac.jp

Name of contact person

1st name	Koichi
Middle name
Last name	Hashimoto

Organization

University of Tsukuba, Tsukuba Clinical Research & Development Organization

Division name

Clinical Research Service Center

Zip code

305-8576

Address

2-1-1 Amakubo, Tsukuba, Ibaraki

TEL

029-853-3326

Homepage URL

Email

koichi.hashimoto@md.tsukuba.ac.jp

Institute

University of Tsukuba

Institute

Department

Personal name

Organization

Ono Pharmaceutical Co., LTD.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

University of Tsukuba Hospital IRB

Address

2-1-1 Amakubo, Tsukuba, Ibaraki

Tel

029-853-3914

Email

chiken@un.tsukuba.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

筑波大学附属病院（茨城）University of Tsukuba Hospital, 北海道大学病院（北海道）Hokkaido University Hospital, 神奈川県立がんセンター（神奈川）Kanagawa Cancer Center, 東北大学病院(宮城）Tohoku University Hospital, 大阪国際がんセンター（大阪） Osaka International Cancer Institute, 京都府立医科大学附属病院（京都） University Hospital Kyoto Prefectural University of Medicine, 岡山大学病院（岡山）Okayama University Hospital, 国立がん研究センター中央病院（東京）National Cancer Center Hospital

Date of disclosure of the study information

2017

Year

07

Month

18

Day

URL releasing protocol

https://pubmed.ncbi.nlm.nih.gov/35462438/

Publication of results

Published

URL related to results and publications

https://pubmed.ncbi.nlm.nih.gov/35462438/

Number of participants that the trial has enrolled

17

Results

The best response was PR (based on RECIST guideline 1.1) in 1 patient.
The response has continued to end of trial.
Objective response rate were 5.9%, lower than the threshold response rate of 5%.

Results date posted

2023

Year

06

Month

02

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Patients aged 18 and over
Unresectable advanced germ cell tumors refractory to second-line or further chemotherapy

Participant flow

1)Informed Consent
2)Screening (Confirmation of inclusion/exclusion criteria)
3) Start of study drug administration (Nivolumab was administered over 30 min at 240 mg/body every 2 weeks.)
4) Treatments were continued until disease progression or intolerable adverse event(AE) occurrence.
5) The study participants will be observed until death

Adverse events

Incidence of AEs associated with Nivolumab
1 death case of SAE (malignant neoplasm progression) associated with Nivolumab
2 cases of AEs leading to treatment discontinuation (1 case of malignant neoplasm progression)

Outcome measures

Objective response rate, central review

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

06

Month

01

Day

Date of IRB

2017

Year

06

Month

16

Day

Anticipated trial start date

2017

Year

07

Month

18

Day

Last follow-up date

2021

Year

05

Month

21

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

07

Month

14

Day

Last modified on

2023

Year

06

Month

02

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032327