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

Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01069653
• Other study ID #: SUMS-21-74
• Secondary ID: UMIN000003191
• Status: Completed
• Phase: Phase 1
• Start date: February 2010
• Est. completion date: March 2019

Study information

• Verified date: March 2019
• Source: Shiga University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 85 Years

Eligibility

Inclusion Criteria:

1. SCLC that can not undergo curative surgery and treatment, and is refractory to standard chemotherapy and radiotherapy

2. ECOG performance status 0-2

3. Age between 20 to 85

4. Clinical efficacy can be evaluated by some methods

5. No prior chemotherapy, radiation therapy, hyperthermia or immunotherapy within 4 weeks

6. Life expectancy > 3 months

7. 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

8. HLA-A*2402

9. Able and willing to give valid written informed consent

Exclusion Criteria:

1. Active and uncontrolled cardiac disease (i.e. coronary syndromes, arrhythmia)

2. Myocardial infarction within six months before entry

3. Breastfeeding and Pregnancy (woman of child bearing potential)

4. Active and uncontrolled infectious disease

5. Concurrent treatment with steroids or immunosuppressing agent

6. Other malignancy requiring treatment

7. Non-cured traumatic wound

8. Decision of unsuitableness by principal investigator or physician-in-charge

Related Conditions & MeSH terms

• Lung Neoplasms
• Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

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.

Locations

Country	Name	City	State
Japan	Shiga University of Medical Science Hospital	Otsu	Shiga

Sponsors (2)

Lead Sponsor	Collaborator
Shiga University	Human Genome Center, Institute of Medical Science, University of Tokyo

Country where clinical trial is conducted

Japan, 

References & Publications (7)

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. doi: 10.1007/s11748-007-0211-x. Epub 2008 Feb 24. Review. — View Citation

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. doi: 10.1002/ijc.23823. — View Citation

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. — View Citation

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. — View Citation

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. doi: 10.1111/j.1349-7006.2009.01200.x. Epub 2009 May 14. — View Citation

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. doi: 10.1111/j.1349-7006.2008.00844.x. Epub 2008 Apr 30. — View Citation

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 Nov;98(11):1803-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of safety (NCI CTCAE version3): the number of adverse events of vaccination therapy.		2 months
Primary	Evaluation of tolerability (maximum tolerated dose, MTD and dose limiting toxicity, DLT) for the determination of the recommended dose for next phase trial.		2 months
Secondary	Immunological responses: Peptides specific CTL, Antigen cascade, Regulatory T cells, Cancer antigens and HLA levels.		2 months (every time point(s) at which each course is completed)
Secondary	Evaluation of clinical efficacy: Objective response rate (RECIST1.1), Tumor markers, Overall survival, Progression free survival.		2 months (every time point(s) at which each course is completed)