UMIN-CTR Clinical Trial

Public title

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil; OK-432 and Montanide; ISA-51 in patients with cancers expressing NY-ESO-1 antigen

Acronym

A phase I study of cancer vaccine with NY-ESO-1f peptide

Scientific Title

A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil; OK-432 and Montanide; ISA-51 in patients with cancers expressing NY-ESO-1 antigen

Scientific Title:Acronym

A phase I study of cancer vaccine with NY-ESO-1f peptide

Region

Japan

Condition

advanced esophageal cancer, stomach cancer, non-small cell lung cancer (NSCLC), malignant melanoma

Classification by specialty

Gastroenterology	Pneumology	Gastrointestinal surgery
Hepato-biliary-pancreatic surgery	Dermatology

Classification by malignancy

Malignancy

Genomic information

NO

Narrative objectives1

We identified the NY-ESO-1 peptide regions recognized by CD4 and CD8 T cells using an IFN-gamma secretion assay and individual overlapping peptides spanning the entire NY-ESO-1 protein for stimulation. Regions II(73-114) and III (121-144) were frequently recognized by either CD4 or CD8 T cells irrespective of patients' HLA type. Moreover, the most dominant peptide region (91-108) eliciting antibody response was also included in the region II. Based on these findings, we will investigate the safety and immunogenicity of a long peptide spanning a peptide region 91-110 in NY-ESO-1 for vaccine.

Basic objectives2

Safety

Basic objectives -Others

Trial characteristics_1

Confirmatory

Trial characteristics_2

Pragmatic

Developmental phase

Phase I

Primary outcomes

Toxicities and adverse events defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Scale.

Key secondary outcomes

NY-ESO-1 specific immunitywill be assessed using blood obtained at baseline, every visit for vaccination and 4 weeks after the sixth vaccination. NY-ESO-1 reactive antibodies measured by ELISA and cellular immunity by NY-ESO-1 specific CD4 and CD8 T cells by cytokine secretion as determined by FACS analysis will be assayed.
Tumor response will be assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Disease status will be assessed at baseline, week 13, and 4-6 weeks after the sixth vaccination in patients with evaluable (measurable and non-measurable) disease.

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

Vaccine

Interventions/Control_1

NY-ESO-1f peptide (600 µg)+Montanide ISA-51 (1.0 mL)+ K-432 (Picibanil) (0.2 KE)
Every 3 weeks x 6 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

Male and Female

Key inclusion criteria

1.Histological diagnosis of any type of cancers expressing NY-ESO-1 antigen.
2.Advanced cancer patient.
3.Performance status of 0-2.
4.Age 20-80 years.
5.At least 4 weeks since radiotherapy, biological therapy, chemotherapy or surgery prior to first dosing of study agent.
6.Life expectancy > 5 months.
7.Laboratory values within the following limits:
WBC > 3000/mm3
Neutrophil count > 1500/mm3
Hemoglobin> 8.0 g/dL
Platelet count > 100,000/mm3
Serum bilirubin < 2.0 mg/dl
AST,ALT < 150 IU/l
Serum creatmine < 2.0 mg/dL
8.Able and willing to give witnessed, written informed consent for participation in the trial
9.no penicillin allergy

Key exclusion criteria

1.Clinically significant heart disease (i.e., NYHA class 3 congestive heart failure; myocardial infarction within the past six months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
2.Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders.
3.Previous bone marrow or stem cell transplant.
4.History of immunodeficiency disease or autoimmune disease except vitiligo.
5.Metastatic disease to the central nervous system, unless treated and stable.
6.Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ.
7.Known HIV, positivity.
8.Concomitant treatment with steroids. Topical or inhalational steroids are permitted. (See also Section 6.7 for restrictions/recommendations on 'Ancillary Therapy'.)
9.Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dose of study agent.
10.Pregnancy or lactation.
11.Women of childbearing potential not using a medically acceptable means of contraception.
12.Psychiatric or addictive disorders that may compromise the ability to give informed consent.
13.Lack of availability of the patient for immunological and clinical follow-up assessment.

Target sample size

30

Name of lead principal investigator

1st name
Middle name
Last name	Eiichi Nakayama

Organization

Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences

Division name

Department of Immunology

Zip code

Address

2-5-1 Shikata-cho, Okayama 700-8558, Japan

TEL

086-235-7187

Email

nakayama@mw.kawasaki-m.ac.jp

Name of contact person

1st name
Middle name
Last name	Hisashi Wada

Organization

Osaka University Graduate School of Medicine

Division name

Department of Surgery

Zip code

Address

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

TEL

06-6879-3251

Homepage URL

http://www.med.osaka-u.ac.jp/pub/surg2/www/cancer/shokudo/shugakuchiryo/ny-eso.html

Email

hwada@gesurg.med.osaka-u.ac.jp

Institute

Department of Immunology
Okayama University Graduate School of
Medicine, Dentistry and Pharmaceutical Sciences

Institute

Department

Personal name

Organization

Ludwig Institute for Cancer Research, NY, USA

Organization

Division

Category of Funding Organization

Outside Japan

Nationality of Funding Organization

USA

Co-sponsor

Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine

Department of Immunotherapeutics (Medinet) Graduate School of Medicine
The University of Tokyo

Name of secondary funder(s)

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

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

川崎医科大学附属病院（岡山県）、大阪大学医学部附属病院（大阪府）、東京大学医学部附属病院（東京都）

Date of disclosure of the study information

2008

Year

07

Month

24

Day

URL releasing protocol

http://onlinelibrary.wiley.com/doi/10.1002/ijc.25955/pdf

Publication of results

Published

URL related to results and publications

http://onlinelibrary.wiley.com/doi/10.1002/ijc.25955/pdf

Number of participants that the trial has enrolled

Results

We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 mcg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.

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

2007

Year

12

Month

18

Day

Date of IRB

Anticipated trial start date

2008

Year

02

Month

01

Day

Last follow-up date

2013

Year

12

Month

01

Day

Date of closure to data entry

2013

Year

12

Month

01

Day

Date trial data considered complete

2014

Year

06

Month

30

Day

Date analysis concluded

2014

Year

06

Month

30

Day

Other related information

Registered date

2008

Year

07

Month

22

Day

Last modified on

2014

Year

07

Month

22

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000001534