Clinical trial NCT01003808: Safety Study of a Recombinant Protein Vaccine to Treat Esophageal Cancer
Official title: IMF-001 Phase 1 Study With Refractory Esophageal Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Esophageal Cancer
Lead sponsor: ImmunoFrontier, Inc.
Sponsor class: INDUSTRY
First posted: 2009-10-29
Enrollment: 25
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: First 12 weeks (during the first 6 injections)
Secondary outcomes:
measure: To evaluate clinical activity (tumor response and time to progression).
timeFrame: Up to 2 years, or until progression of PS or no positive immune response from IMF-001.
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
state: Aichi
city: TSU
country: Japan
facility: Mie University Hospital
state: Mie
city: Kitano Hospital
country: Japan
facility: Kitano Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
Study officials:
affiliation: ImmunoFrontier, Inc.
name: Daiju Ichimaru, BSc
role: STUDY_DIRECTOR
References:
citation: 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.
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.
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.
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.
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. doi: 10.1002/ijc.22583.
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. doi: 10.1158/1078-0432.CCR-05-1900.
citation: Kageyama S, Wada H, Muro K, Niwa Y, Ueda S, Miyata H, Takiguchi S, Sugino SH, Miyahara Y, Ikeda H, Imai N, Sato E, Yamada T, Osako M, Ohnishi M, Harada N, Hishida T, Doki Y, Shiku H. Dose-dependent effects of NY-ESO-1 protein vaccine complexed with cholesteryl pullulan (CHP-NY-ESO-1) on immune responses and survival benefits of esophageal cancer patients. J Transl Med. 2013 Oct 5;11:246. doi: 10.1186/1479-5876-11-246.