UMIN-CTR Clinical Trial

Public title

Open-label clinical study for safety and preliminary efficacy of HiDCV-OS1 Hybrid cell (dendritic and tumor fusion cells) and subsequent subcutaneous administration of GEN0101 in patients with recalcitrant residual or relapsed ovarian cancer after strict chemotherapy.

Acronym

Phase I safety and preliminary efficacy study of HiDCV-OS1 and GEN0101 against the patients suffering from chemotherapy-resistant ovarian cancer.

Scientific Title

Open-label clinical study for safety and preliminary efficacy of HiDCV-OS1 Hybrid cell (dendritic and tumor fusion cells) and subsequent subcutaneous administration of GEN0101 in patients with recalcitrant residual or relapsed ovarian cancer after strict chemotherapy.

Scientific Title:Acronym

Phase I safety and preliminary efficacy study of HiDCV-OS1 and GEN0101 against the patients suffering from chemotherapy-resistant ovarian cancer.

Region

Japan

Condition

Ovarian cancer

Classification by specialty

Obstetrics and Gynecology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

We will evaluate the safety and efficacy of novel immunotherapy which is the combination of HiDCV-OS1 (dendritic and tumor fusion cells) and GEN0101 against the patients suffering from recalcitrant residual or relapsed ovarian cancer after strict chemotherapy.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Phase I

Primary outcomes

Safety: Adverse events during the clinical trial

Key secondary outcomes

Responsibility
Induction of antitumor immunity
Tumor marker

Adverse events due to apheresis.
Blood level of anti-HVJ-E antibody, and antinuclear antibody

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

Other

Interventions/Control_1

The single injection of HiDCV-OS1 and 3 times subsequent injection of GEN010 will be done in the 10 days.
This procedure is set as 1 cycle.
In the first 10 days, four times administration of drugs will be done, and then, drug holidays will be done for 18 days.
This cycle will be repeated 2 times.

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

20

years-old

<=

Age-upper limit

80

years-old

>=

Gender

Female

Key inclusion criteria

Primary registration
1) Patients providing a written informed consent to participate in this clinical study by voluntary agreement based on his will.
2) Patients proving a written informed consent to use ovarian cancer tissue obtained by operation etc. for making the fusion cell.
3) Age over 20 and less than or equal to 80 years old at the time of informed consent.
4) Have a diagnosis of ovarian carcinoma as confirmed by histology.
5) Clinical stage III or IV by FIGO2014.
6) No medical history of chemotherapy against ovarian cancer, and plant to have chemotherapy in the near future.
7) ECOG Performance Status 0 or 1.
8) The marrow, the liver or the kidney does not have serious disfunctions.

Secondary registration
1) Patients providing a written informed consent to have the HiDCV-OS1 Hybrid cell therapy by voluntary agreement based on his will.
2) Prepared HiDCV-OS-1 hybrid cells compatible with appropriateness criteria.
3) Patients treated surgically for primary or metastatic lesion of ovarian cancer before or after the primary registration.
4) Patients treated with chemotherapy less than or equal to three regimens including the platinum drugs before the secondary registration, and following (1) or (2).
(1)Evaluated PD after previous chemotherapy.
Evaluated SD, and medical doctor diagnosed that chemotherapy was difficult to continue due to severe adverse events.
Or
Evaluated SD, and medical doctor diagnosed chemotherapy had no effect because of tumor progression.
(2) Patients had relapsed ovarian cancer recognized by imaging test within 6 months after chemotherapy.
5) The marrow, the liver or the kidney does not have serious disfunctions.
6) ECOG Performance Status <= 2.

Key exclusion criteria

Primary registration
1) Brain metastasis
2) Serious complications such as uncontrolled active infection
3) Medical history of other malignancy, except for the relapse-free and metastasis-free for more than 2 years after the last treatment at the registration
4) Active autoimmune disease
5) Receiving systemic administration of glucocorticosteroid which restrains immunity response except low dose of oral predonisone.
6) PT(%) less than 63% or APTT more than 58.5 sec at the screening visit
7) Positive result of the HCV antibody, HBV, HIV, or HTLV-I test at the screening visit
8) Inappropriate to be enrolled in this study judged by the investigators

Secondary registration
1) Withdraw the agreement after the primary registration.
2) Positive for skin prick test of GEN0101.
3) Brain metastasis.
4) Other malignancy after the primary registration.
5) Serious complications such as uncontrolled active infection.
6) Receiving systemic administration of glucocorticosteroid which restrains immunity response except low dose of oral predonisone.
7) PT(%) less than 63% or APTT more than 58.5 sec at the screening visit.
8) Administered with unapproved drug within 4 weeks before the secondary registration.
9) Inappropriate to be enrolled in this study judged by the investigators.

Target sample size

6

Name of lead principal investigator

1st name	Tadashi
Middle name
Last name	Kimura

Organization

Osaka University Graduate School of Medicine

Division name

Department of Obstetrics and Gynecology

Zip code

565-0871

Address

2-2, Yamadaoka, Suita, Osaka 565-0871, Japan

TEL

06-6879-3351

Email

tadashi@gyne.med.osaka-u.ac.jp

Name of contact person

1st name	Kenjiro
Middle name
Last name	Sawada

Organization

Osaka University Graduate School of Medicine

Division name

Department of Obstetrics and Gynecology

Zip code

565-0871

Address

2-2, Yamadaoka, Suita, Osaka 565-0871, Japan

TEL

06-6879-3351

Homepage URL

Email

daasawada@gyne.med.osaka-u.ac.jp

Institute

Osaka University Graduate School of Medicine

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Government offices of other countries

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

The First Certified Special Committee for Regenerative Medicine, Osaka University

Address

2-2, Yamadaoka, Suita, Osaka 565-0871, Japan

Tel

06-6210-8293

Email

nintei@dmi.med.osaka-u.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

大阪大学医学部附属病院（大阪府)

Date of disclosure of the study information

2018

Year

02

Month

13

Day

URL releasing protocol

Publication of results

Published

URL related to results and publications

Number of participants that the trial has enrolled

6

Results

None of grade >=3 TEAE whose causal relationship with the treatment cannot be ruled out were reported, and the treatment was indicated to some extent to be tolerable.In cytoreductive effects, there were no cases that could obtain CR or PR. However, the induction of tumor immunity and the reduction of tumor marker level were observed in some cases. Although the conclusive judgment may be impossible from such small cases, tumor immunity could possibly be induced by the protocol treatment in this study.

Results date posted

2023

Year

08

Month

07

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

All patients are female, and 2 were 50s, 1 was 60s, and the other was 70s.Stages of the disease: 3 were 3C, and the other was 4 B. Uncontrolled study.

Participant flow

In May 2018, the consent was acquired from the first patient. Consent acquisition: 12, 1st screening failure: 2, and primary registration:10. Among them, four patients with relapse/recurrence during the study period were secondarily registered and received the study treatment. All four completed the protocol treatment.In September 2022, after the last observation of the fourth patient, this study was stopped.
All of the four participants were included in the analysis object both in efficacy and in safety.

Adverse events

No severe diseases were observed. Nonsevere diseases: neutropenia with grade 2:1/4(25%), and elevation of serum amylase with grade 1: 1/4(25%) observed in one case.

Outcome measures

Plan to share IPD

none

IPD sharing Plan description

none

Recruitment status

Completed

Date of protocol fixation

2018

Year

01

Month

15

Day

Date of IRB

2018

Year

01

Month

23

Day

Anticipated trial start date

2018

Year

04

Month

02

Day

Last follow-up date

2023

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2018

Year

02

Month

13

Day

Last modified on

2023

Year

08

Month

07

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035704