UMIN-CTR Clinical Trial

Basic information
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
Condition	colorectal cancer patients refractory to conventional treatments
Classification by specialty	Gastroenterology
Classification by malignancy	Malignancy
Genomic information	NO

Objectives
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

Assessment
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) .

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
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

Public contact
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

Sponsor
Institute	Kurume University Cancer Vaccine Center
Institute
Department

Funding Source
Organization	The Ministry of Education, Culture, Sports, Science, and Technology, Japan
Organization
Division
Category of Funding Organization
Nationality of Funding Organization	Japan

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

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

Other administrative information
Date of disclosure of the study information	2012 Year 03 Month 13 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
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	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
Other related information

Management information
Registered date	2012 Year 03 Month 13 Day
Last modified on	2020 Year 09 Month 23 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000008843