Clinical trial NCT01592617: Phase II Study of S-488410 to Treat Non-small Cell Lung Cancer
Official title: Phase II Study of Peptide Cancer Vaccine S-488410 to Treat Advanced Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: cancer vaccine
HLA-A*24:02
lung cancer
CTL
Lead sponsor: Shiga University
Sponsor class: OTHER
Collaborators: name: Showa University
name: Fukushima Medical University
name: Tohoku University
name: Shionogi
name: Tokyo University
name: University of Chicago
First posted: 2012-05-07
Enrollment: 45
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators identified three cancer-testis antigens, as targets for cancer vaccination against lung cancer. In this clinical study, the investigators examine using a combination of three peptides from these three antigens (S-488410) the safety, immunogenicity, and antitumor effect of vaccine treatment for advanced non-small cell lung cancer patients.

Detailed description: The purpose of this study is to evaluate the clinical efficacy and safety of S-488410 for advanced non-small cell lung cancers who failed to standard therapy.

The investigators previously identified three novel HLA-A\*2402-restricted epitope peptides, which were derived from three cancer-testis antigens, as targets for cancer vaccination against lung cancer. In this phase II trial, we examine using a combination of these three 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 criteria: Inclusion Criteria:

* Advanced NSCLC that cannot undergo curative surgery.
* Patients that are refractory to standard chemotherapy or cannot be treated with further therapy due to severe adverse effects of chemotherapy.
* Histologically diagnosed NSCLC.
* Clinical efficacy can be evaluated by radiologic methods within 4 weeks prior to receiving treatment.
* ECOG performance status 0-2 within 2 weeks prior to receiving treatment.
* Life expectancy \> 3 months.
* Age between 20 to 79
* Male or Female.
* In patients or out patients.
* Able and willing to give valid written informed consent.

Exclusion Criteria:

* Other malignancy requiring treatment
* radiation, immunotherapy, hyperthermia, or surgery.
* Active and uncontrolled infectious disease
* Active and uncontrolled hepatic dysfunction, kidney dysfunction, cardiac disease, or lung disease (i.e. interstitial pneumonia).
* Autoimmune disease.
* HIV-Ab or antigen positive
* Prior anti-cancer therapy within 4 weeks
* Laboratory values as follows: 2000\<mm3 \< WBC \< 15000/mm3, Platelet count \< 50000/mm3, Asparate transaminase \> 5 X cutoff value, Alanine transaminase \> 5 X cutoff value, Total bilirubin \> 3 X cutoff value, and Serum creatinine \> 3X cutoff value.
* Patients knows HLA-A type.
* Breastfeeding and Pregnancy (woman of child bearing potential)
* Refusal of pregnancy conception.
* Treated with S-488401, S-488402, or S-488403.
* Treated with other investigational drug within 3 months prior to receiving S-48810 treatment.
* Decision of nonenrollment of the patients by principal investigator or physician-in-charge from the view point of patient's safety.

Primary outcomes:
measure: Evaluation of difference in overall survival after vaccination therapy between HLA-A 24:02 and non-HLA-A 24:02 patients.
timeFrame: Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year.
Secondary outcomes:
measure: CTL response between HLA-A24:02 and non-HLA-A24:02
timeFrame: Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year.
measure: PFS and ORR between HLA-A24:02 and non-HLA-A24:02
timeFrame: Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year.
measure: PFS and OS between CTL response positive and negative
timeFrame: Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year.
measure: Safety and tolerability: Number of Adverse Events with information of disease, grade and incidence
timeFrame: Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year.
measure: Identification of biomarkers for efficacy and safety that are mentioned above
timeFrame: Participants will be followed for the duration of vaccination therapy, an expected average of more than 1 year.
Other outcomes:
Locations:
city: Otsu
country: Japan
facility: Department of Medical Oncology, Shiga University of Medical Science Hospital
state: Shiga
Study officials:
affiliation: Department of Medical Oncology, Shiga University of Medical Science
name: Yataro Daigo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
citation: 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.
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. doi: 10.1158/0008-5472.CAN-07-3243.
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. doi: 10.1111/j.1349-7006.2007.00603.x.
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. doi: 10.1158/0008-5472.CAN-06-2137.