Safety Study of a Recombinant Protein Vaccine to Treat Esophageal Cancer

• ClinicalTrials.gov Identifier: NCT01003808
• Recruitment Status: Completed
• First Posted: October 29, 2009
• Last Update Posted: April 17, 2013
• Sponsor: ImmunoFrontier, Inc.
• Information provided by (Responsible Party): ImmunoFrontier, Inc.

Tracking Information

• First Submitted Date: October 16, 2009
• First Posted Date: October 29, 2009
• Last Update Posted Date: April 17, 2013
• Study Start Date: November 2009
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 28, 2009): 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. [ Time Frame: First 12 weeks (during the first 6 injections) ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: October 28, 2009): To evaluate clinical activity (tumor response and time to progression). [ Time Frame: Up to 2 years, or until progression of PS or no positive immune response from IMF-001. ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety Study of a Recombinant Protein Vaccine to Treat Esophageal Cancer
• Official Title: IMF-001 Phase 1 Study With Refractory Esophageal Tumor
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Esophageal Cancer

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).

Other Name: CHP-NY-ESO-1

Study Arms

Experimental: 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).

Intervention: Biological: IMF-001

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 16, 2013): 25
• Original Estimated Enrollment (submitted: October 28, 2009): 20
• Actual Study Completion Date: December 2012
• Actual Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT01003808
• Other Study ID Numbers: IMF001J
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: ImmunoFrontier, Inc.
• Study Sponsor: ImmunoFrontier, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Daiju Ichimaru, BSc; ImmunoFrontier, Inc.

• PRS Account: ImmunoFrontier, Inc.
• Verification Date: April 2013