Safety Study of Peptide Cancer Vaccine To Treat HLA-A*24-positive Advanced Small Cell Lung Cancer - Full Text View

Purpose

The purpose of this study is to evaluate the safety, tolerability, immune response and clinical efficacies of HLA-A*2402 restricted epitope peptides CDCA1 and KIF20A emulsified with Montanide ISA 51 for advanced small cell lung cancers.

Condition	Intervention	Phase
Small Cell Lung Cancer	Biological: HLA-A*2402-restricted CDCA1 and KIF20A peptides	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Cancer Vaccine Therapy Using Epitope Peptide Restricted to HLA-A*24 (CDCA1,KIF20A) in Patients With Small Cell Lung Cancer Refractory to Standard Therapy

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

U.S. FDA Resources

Further study details as provided by Shiga University:

Primary Outcome Measures:

Evaluation of safety (NCI CTCAE version3): the number of adverse events of vaccination therapy. [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
Evaluation of tolerability (maximum tolerated dose, MTD and dose limiting toxicity, DLT) for the determination of the recommended dose for next phase trial. [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immunological responses: Peptides specific CTL, Antigen cascade, Regulatory T cells, Cancer antigens and HLA levels. [ Time Frame: 2 months (every time point(s) at which each course is completed) ] [ Designated as safety issue: No ]
Evaluation of clinical efficacy: Objective response rate (RECIST1.1), Tumor markers, Overall survival, Progression free survival. [ Time Frame: 2 months (every time point(s) at which each course is completed) ] [ Designated as safety issue: No ]

Estimated Enrollment:	9
Study Start Date:	February 2010
Estimated Study Completion Date:	October 2013
Estimated Primary Completion Date:	October 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: CDCA1-KIF20A-1mg Patients will be vaccinated once a week for four weeks of a treatment cycle. On each vaccination day, the HLA-A*2402-restricted CDCA1 peptide (1mg) and KIF20A peptide(1mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection.	Biological: HLA-A*2402-restricted CDCA1 and KIF20A peptides Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg. Other Name: CDCA1 and KIF20A
Experimental: CDCA1-KIF20A-2mg Patients will be vaccinated once a week for four weeks of a treatment cycle. On each vaccination day, the HLA-A*2402-restricted CDCA1 peptide (2mg) and KIF20A peptide(2mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection.	Biological: HLA-A*2402-restricted CDCA1 and KIF20A peptides Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg. Other Name: CDCA1 and KIF20A
Experimental: CDCA1-KIF20A-3mg Patients will be vaccinated once a week for four weeks of a treatment cycle. On each vaccination day, the HLA-A*2402-restricted CDCA1 peptide (3mg) and KIF20A peptide(3mg) mixed with Montanide ISA 51 will be administered by subcutaneous injection.	Biological: HLA-A*2402-restricted CDCA1 and KIF20A peptides Escalating doses of every peptide will be administered by subcutaneous injection on days 1, 8, 15 and 22 of each treatment cycle. Planned doses of peptides are 1.0mg, 2.0mg and 3.0mg. Other Name: CDCA1 and KIF20A

Detailed Description:

The investigators previously identified three novel HLA-A*2402-restricted epitope peptides, which were derived from two cancer-testis antigens, CDCA1 and KIF20A, as targets for cancer vaccination against lung cancer. In this phase I trial, the investigators examine using a combination of these two peptides the safety, immunogenicity, and antitumor effect of vaccine treatment for HLA-A*2402-positive advanced small cell lung cancer patients who failed to standard therapy.

Eligibility

Ages Eligible for Study:	20 Years to 85 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

SCLC that can not undergo curative surgery and treatment, and is refractory to standard chemotherapy and radiotherapy
ECOG performance status 0-2
Age between 20 to 85
Clinical efficacy can be evaluated by some methods
No prior chemotherapy, radiation therapy, hyperthermia or immunotherapy within 4 weeks
Life expectancy > 3 months
Laboratory values as follows 1500/mm3 < WBC < 15000/mm3 Platelet count > 75000/mm3 Asparate transaminase < 3 X cutoff value Alanine transaminase < 3 X cutoff value Total bilirubin < 3 X cutoff value Serum creatinine < 2X cutoff value
HLA-A*2402
Able and willing to give valid written informed consent

Exclusion Criteria:

Active and uncontrolled cardiac disease (i.e. coronary syndromes, arrhythmia)
Myocardial infarction within six months before entry
Breastfeeding and Pregnancy (woman of child bearing potential)
Active and uncontrolled infectious disease
Concurrent treatment with steroids or immunosuppressing agent
Other malignancy requiring treatment
Non-cured traumatic wound
Decision of unsuitableness by principal investigator or physician-in-charge

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01069653

Contacts

Contact: Yataro Daigo, MD, PhD

81-77-548-2111

ydaigo@belle.shiga-med.ac.jp

Locations

Japan
Shiga University of Medical Science Hospital	Recruiting
Otsu, Shiga, Japan, 520-2192
Contact: Yataro Daigo, MD, PhD 81-77-548-2111 ydaigo@belle.shiga-med.ac.jp

Sponsors and Collaborators

Shiga University

Human Genome Center, Institute of Medical Science, University of Tokyo

Investigators

Principal Investigator:

Yataro Daigo, MD, PhD

Department of Medical Oncology, Shiga University of Medical Science

More Information

Publications:

Kono K, Mizukami Y, Daigo Y, Takano A, Masuda K, Yoshida K, Tsunoda T, Kawaguchi Y, Nakamura Y, Fujii H. Vaccination with multiple peptides derived from novel cancer-testis antigens can induce specific T-cell responses and clinical responses in advanced esophageal cancer. Cancer Sci. 2009 Aug;100(8):1502-9. Epub 2009 May 14.

Harao M, Hirata S, Irie A, Senju S, Nakatsura T, Komori H, Ikuta Y, Yokomine K, Imai K, Inoue M, Harada K, Mori T, Tsunoda T, Nakatsuru S, Daigo Y, Nomori H, Nakamura Y, Baba H, Nishimura Y. HLA-A2-restricted CTL epitopes of a novel lung cancer-associated cancer testis antigen, cell division cycle associated 1, can induce tumor-reactive CTL. Int J Cancer. 2008 Dec 1;123(11):2616-25.

Mizukami Y, Kono K, Daigo Y, Takano A, Tsunoda T, Kawaguchi Y, Nakamura Y, Fujii H. Detection of novel cancer-testis antigen-specific T-cell responses in TIL, regional lymph nodes, and PBL in patients with esophageal squamous cell carcinoma. Cancer Sci. 2008 Jul;99(7):1448-54. Epub 2008 Apr 30.

Daigo Y, Nakamura Y. From cancer genomics to thoracic oncology: discovery of new biomarkers and therapeutic targets for lung and esophageal carcinoma. Gen Thorac Cardiovasc Surg. 2008 Feb;56(2):43-53. Epub 2008 Feb 24. Review.

Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, Miyagi Y, Nakayama H, Fujita M, Hosokawa M, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007 Dec 15;67(24):11601-11.

Suda T, Tsunoda T, Daigo Y, Nakamura Y, Tahara H. Identification of human leukocyte antigen-A24-restricted epitope peptides derived from gene products upregulated in lung and esophageal cancers as novel targets for immunotherapy. Cancer Sci. 2007 Sep 2; [Epub ahead of print]

Hayama S, Daigo Y, Kato T, Ishikawa N, Yamabuki T, Miyamoto M, Ito T, Tsuchiya E, Kondo S, Nakamura Y. Activation of CDCA1-KNTC2, members of centromere protein complex, involved in pulmonary carcinogenesis. Cancer Res. 2006 Nov 1;66(21):10339-48.

Responsible Party:	Yataro Daigo, Professor, Director of Cancer Center, Shiga University
ClinicalTrials.gov Identifier:	NCT01069653 History of Changes
Other Study ID Numbers:	SUMS-21-74, UMIN000003191
Study First Received:	February 16, 2010
Last Updated:	May 5, 2012
Health Authority:	Japan: Ministry of Health, Labor and Welfare

Keywords provided by Shiga University:

CDCA1
KIF20A
lung cancer
vaccine
HLA-A*2402

Additional relevant MeSH terms:

Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site

Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms

ClinicalTrials.gov processed this record on May 23, 2013