UMIN-CTR Clinical Trial

Public title

Phase I Clinical trial of personalized peptide vaccine in combination with humanized anti-IL6 receptor monoclonal antibody for refractory colorectal cancer patients

Acronym

Clinical trial of peptide vaccine in combination with anti-IL6 receptor antibody for refractory colorectal cancer patients

Scientific Title

Phase I Clinical trial of personalized peptide vaccine in combination with humanized anti-IL6 receptor monoclonal antibody for refractory colorectal cancer patients

Scientific Title:Acronym

Clinical trial of peptide vaccine in combination with anti-IL6 receptor antibody for refractory colorectal cancer patients

Region

Japan

Condition

colorectal cancer patients refractory to conventional treatments

Classification by specialty

Gastroenterology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

The aims of this trial are to evaluate safety of personalized peptide vaccine in combination with anti-IL6 receptor antibody and to examine the specific immunological responses to vaccine for determining an optimal dose of anti-IL6 receptor antibody in refractory colorectal cancer patients, who showed elevated plasma IL-6 more than 3 pg/ml.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I

Primary outcomes

Safety (adverse events) of personalized peptide vaccine in combination with anti-IL6 receptor antibody.

Key secondary outcomes

Specific immunological responses after peptide vaccine (anti-peptide IgG titers in plasma and peptide-specific CTL responses in PBMC) .

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Dose comparison

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Vaccine

Interventions/Control_1

Anti-IL6 receptor antibody [Actemra (tocilizumab), Chugai Pharmaceutical Co; 0.5mg/kg (n=6), 2mg/kg (n=6), or 8mg/kg (n=6)] is intravenously administrated. After three days, a maximum of 4 peptides (3 mg/each peptide), which are selected based on the results of HLA typing and peptide-specific IgG titers, are subcutaneously administrated with incomplete Freund's adjuvant (Montanide ISA51, Seppic)once a week for consecutive 6 weeks. During the treatment, safety is evaluated.The dose of anti-IL6 receptor antibody is escalated, if the safty is confirmed in 6 independent patients at the same dose.

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

Not applicable

Gender

Male and Female

Key inclusion criteria

The subjects must satisfy the following conditions.
1)Patients must be pathologically diagnosed as colorectal cancer, and refractory to conventional treatments. Target lesions for response evaluation are not essential. The term for wash out of previous treatments should be basically more than 4 weeks, and patients must show no clinical effects or adverse events of previous treatments.
2) Patients must show an elevation of plasma IL-6 more than 3 pg/ml before treatment.
3) Patients must be an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4) Patients must be a positive status for HLA-A2, -A3, -A11, -A24, -A26, -A31, or -A33.
6) Patients must possess positive IgG responses to at least two of the different vaccine candidate peptides in pre-treatment plasma.
4) Patients must have a life expectancy of at least 12 weeks.
6) Patients must satisfy the followings:
WBC is between 3,000/mm3 and 9,000/mm3.
Lymphocyte is more than 1,000/mm3
Hb is more than 8.0g/dl
Platelet is more than 120,000/mm3
Serum Creatinine is less than 1.5 times upper limit of normal.
Total Bilirubin, AST, and ALT are less than 2 times upper limit of normal.
8) Patients must be over 20 years old.
9) Written informed consent must be obtained from patients.

Key exclusion criteria

The following patients must be excluded:
1) Patients with severe underlying diseases (active and severe infectious diseases, activa tuberculosis, circulatory diseases, respiratory diseases, renal diseases, immunodeficiency, disturbance of coagulation, etc).
2) Patients with active interstitial pneumonia or its past history.
3) Patients with active double cancer [synchronic double cancer or asynchronous double cancer with no more than 5-year disease-free period, excluding carcinoma in situ (lesions equal to intraepithelial or intramucosal cancer) judged to have been cured by local treatment].


4) Patients with the past history of severe allergic reactions.
5) Patients with Castleman's disease, rheumatoid arthritis, or juvenile idiopathic arthritis or with the past history of them.
6) Patients with the past history of previous tretamnet with anti-IL-6 receptor antibody.
7) Patients with the past history of previous tretament with personalized peptide vaccine developed by Kurume University.
8) Pregnant, nursing, or who wants pregnancy. Patients with no acceptance of effective contraception during and for at least 70 days after study participation.
9) Patients with other inappropriate conditions for enrollment judged by the clinicians.

Target sample size

18

Name of lead principal investigator

1st name
Middle name
Last name	Teturou Sasada

Organization

Kurume University

Division name

Department of Immunology

Zip code

Address

Asahi-machi 67, Kurume, Fukuoka 830-0011

TEL

0942-31-7551

Email

tsasada@med.kurume-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Akira Yamada

Organization

Kurume University

Division name

Research Center for Innovative Cancer Therapy, Cancer Vaccine Development Division

Zip code

Address

Asahi-machi 67, Kurume, Fukuoka 830-0011, Japan

TEL

0942-31-7744

Homepage URL

Email

akiymd@med.kurume-u.ac.jp

Institute

Kurume University Cancer Vaccine Center

Institute

Department

Personal name

Organization

The Ministry of Education, Culture, Sports, Science, and Technology, Japan

Organization

Division

Category of Funding Organization

Nationality of Funding Organization

Japan

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

Date of disclosure of the study information

2012

Year

03

Month

13

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

Terminated

Date of protocol fixation

2012

Year

02

Month

23

Day

Date of IRB

2012

Year

02

Month

24

Day

Anticipated trial start date

2012

Year

03

Month

01

Day

Last follow-up date

2017

Year

02

Month

28

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2012

Year

03

Month

13

Day

Last modified on

2020

Year

09

Month

23

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000008843