Safety Study of a Recombinant Protein Vaccine to Treat Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

IMF-001 Phase 1 Study With Refractory Esophageal Tumor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01003808
• Other study ID #: IMF001J
• Status: Completed
• Phase: Phase 1
• First received: October 16, 2009
• Last updated: April 16, 2013
• Start date: November 2009
• Est. completion date: December 2012

Study information

• Verified date: April 2013
• Source: ImmunoFrontier, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Pharmaceuticals and Medical Devices Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the biological recommended dose of IMF-001.

Description:

The prognosis of esophageal cancer is improved with the improvement of surgery, chemotherapy and radiation therapy. However, there are no standard therapies established for recurrent esophageal cancer. NY-ESO-1 antigen is expressed in 33% of patients. NY-ESO-1 protein is applicable without limitation by HLA types, and injected as a complex with cholesteryl pullulan (CHP), forming nano-particles (IMF-001), it can activate both CD4+ and CD8+ T cells. In this phase 1 study, the safety and the biological recommended dose will be determined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Radically unresectable stage III/IV esophageal tumors that have failed the standard treatment (including chemotherapy and radiotherapy), recurrent metastasis after radical surgery and not responding to the standard treatments, or recurrent metastasis after radiotherapy before/after radical surgery.

• Primary esophageal tumors confirmed by pathological diagnosis

• Tumor cells expressing NY-ESO-1 antigen (by tissue-immunostaining method or quantitative RT-PCR method)

• Performance status (PS) of 0, 1 or 2 (ECOG Scale)

• Life expectancy >/= 4 months

• No serious disorders with major organs (bone marrow, heart, lung, liver and kidney) and meets the following criteria:

• WBC count >/= 2.0 x 10 9/L

• Hemoglobin >/=8.0g/dL

• Platelet count >/=75 x 10 9/L

• Serum total bilirubin: </=1.5 x ULN (3 x ULN if with liver mets)

• AST and ALT: </=2.5 x ULN (5x ULN if with liver mets)

• Serum creatinine: </=1.5x ULN

• Agree to use birth control including condoms from the time of obtaining the consent to 6 months after the final administration of the study drug [except females after menopause (1 year or more after the last menstruation and females/males after an operation for sterilization)]

• Given written informed consent

Exclusion Criteria:

• HIV antibody positive

• Double cancer

• History of autoimmune disease

• History of severe anaphylaxis

• Active metastatic disease in the central nervous system (CNS) Within 4 weeks after treatment with an anti-tumor agent, systemically administered adrenocorticosteroids, immune suppressants or immune enhancers

• Pregnant or lactating

• Any other inadequacy for this study

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Biological:
• IMF-001
100 or 200 mcg, subcutaneously every 2 weeks. Number of Injections: 6 times. (The treatment may be continued if it is beneficial to the subject).

Locations

Country	Name	City	State
Japan	Kitano Hospital	Kitano Hospital	Osaka
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Osaka University Hospital	Suita	Osaka
Japan	Mie University Hospital	TSU	Mie

Sponsors (1)

Lead Sponsor	Collaborator
ImmunoFrontier, Inc.

Country where clinical trial is conducted

Japan, 

References & Publications (6)

Aoki M, Ueda S, Nishikawa H, Kitano S, Hirayama M, Ikeda H, Toyoda H, Tanaka K, Kanai M, Takabayashi A, Imai H, Shiraishi T, Sato E, Wada H, Nakayama E, Takei Y, Katayama N, Shiku H, Kageyama S. Antibody responses against NY-ESO-1 and HER2 antigens in patients vaccinated with combinations of cholesteryl pullulan (CHP)-NY-ESO-1 and CHP-HER2 with OK-432. Vaccine. 2009 Nov 16;27(49):6854-61. doi: 10.1016/j.vaccine.2009.09.018. Epub 2009 Sep 15. — View Citation

Harada N, Hoshiai K, Takahashi Y, Sakaguchi Y, Kuno T, Hishida T, Shiku H. Preclinical safety pharmacology study of a novel protein-based cancer vaccine CHP-NY-ESO-1. Kobe J Med Sci. 2008 May 23;54(1):E23-34. — View Citation

Hasegawa K, Noguchi Y, Koizumi F, Uenaka A, Tanaka M, Shimono M, Nakamura H, Shiku H, Gnjatic S, Murphy R, Hiramatsu Y, Old LJ, Nakayama E. In vitro stimulation of CD8 and CD4 T cells by dendritic cells loaded with a complex of cholesterol-bearing hydrophobized pullulan and NY-ESO-1 protein: Identification of a new HLA-DR15-binding CD4 T-cell epitope. Clin Cancer Res. 2006 Mar 15;12(6):1921-7. — View Citation

Kawabata R, Wada H, Isobe M, Saika T, Sato S, Uenaka A, Miyata H, Yasuda T, Doki Y, Noguchi Y, Kumon H, Tsuji K, Iwatsuki K, Shiku H, Ritter G, Murphy R, Hoffman E, Old LJ, Monden M, Nakayama E. Antibody response against NY-ESO-1 in CHP-NY-ESO-1 vaccinated patients. Int J Cancer. 2007 May 15;120(10):2178-84. — View Citation

Tsuji K, Hamada T, Uenaka A, Wada H, Sato E, Isobe M, Asagoe K, Yamasaki O, Shiku H, Ritter G, Murphy R, Hoffman EW, Old LJ, Nakayama E, Iwatsuki K. Induction of immune response against NY-ESO-1 by CHP-NY-ESO-1 vaccination and immune regulation in a melanoma patient. Cancer Immunol Immunother. 2008 Oct;57(10):1429-37. doi: 10.1007/s00262-008-0478-5. Epub 2008 Mar 1. — View Citation

Uenaka A, Wada H, Isobe M, Saika T, Tsuji K, Sato E, Sato S, Noguchi Y, Kawabata R, Yasuda T, Doki Y, Kumon H, Iwatsuki K, Shiku H, Monden M, Jungbluth AA, Ritter G, Murphy R, Hoffman E, Old LJ, Nakayama E. T cell immunomonitoring and tumor responses in patients immunized with a complex of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein. Cancer Immun. 2007 Apr 19;7:9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the maximum tolerated dose, dose-limiting toxicities, type/frequency/degree of adverse events and NY-ESO-1 antigen-specific immune response of IMF-001 alone in patients with esophageal cancer.		First 12 weeks (during the first 6 injections)	Yes
Secondary	To evaluate clinical activity (tumor response and time to progression).		Up to 2 years, or until progression of PS or no positive immune response from IMF-001.	Yes