Interleukin-12 Gene and in Vivo Electroporation-Mediated Plasmid DNA Vaccine Therapy in Treating Patients With Merkel Cell Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2013 by OncoSec Medical Incorporated
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OncoSec Medical Incorporated
ClinicalTrials.gov Identifier:
NCT01440816
First received: September 23, 2011
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

This phase II trial studies how well giving interleukin-12 gene and in vivo electroporation-mediated plasmid DNA vaccine therapy works in treating patients with Merkel cell cancer. Placing the gene for interleukin-12 into Merkel cells may help the body build an effective defense to kill tumor cells


Condition Intervention Phase
Recurrent Neuroendocrine Carcinoma of the Skin
Stage I Neuroendocrine Carcinoma of the Skin
Stage II Neuroendocrine Carcinoma of the Skin
Stage III Neuroendocrine Carcinoma of the Skin
Stage IV Neuroendocrine Carcinoma of the Skin
Biological: interleukin-12 gene
Biological: electroporation-mediated plasmid DNA vaccine therapy
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intratumoral Injection of Interleukin-12 Plasmid and in Vivo Electroporation in Patients With Merkel Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by OncoSec Medical Incorporated:

Primary Outcome Measures:
  • Proportion of patients who experience at least 2-fold increase in expression of IL-12 protein in the tumor tissue after IT pIL-12 injections and in vivo electroporation [ Time Frame: From baseline to 2-4 weeks after the first injection ] [ Designated as safety issue: No ]
    Patients who experience at least 2-fold increase in the expression of IL-12 protein will be counted as having a successful outcome. Patients who do not experience a 2-fold or greater increase in IL-12 protein levels in the injected tumor tissue will be classified as a failure for analysis purpose. The proportion of successful outcomes in this population will be reported with 90% Wilson (score) binomial confidence interval.


Secondary Outcome Measures:
  • Safety of intratumoral pIL-12 injections and in vivo electroporation in patients with MCC as assessed by the adverse events [ Time Frame: At days 1, 5, and 8; during weeks 3-4; and at 4-8 or 12 weeks ] [ Designated as safety issue: Yes ]
  • Objective responses in injected and non-injected (distant) lesions [ Time Frame: At 2-4 weeks, week 6, and week 12 ] [ Designated as safety issue: No ]
  • Time to relapse or time to progression [ Time Frame: At 2-4 weeks, week 6, and week 12 ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: At 4-8 or 12 weeks and then annually for up to 5 years ] [ Designated as safety issue: No ]
  • Immunologic effects of IT pIL-12 injection and in vivo EP [ Time Frame: At baseline and 2-4 weeks after the first injection ] [ Designated as safety issue: No ]

Estimated Enrollment: 15
Study Start Date: November 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gene therapy)
Patients receive interleukin-12 gene IT and undergo electrical discharge around the tumor site for electroporation-mediated plasmid DNA vaccine therapy on days 1, 5, and 8. Patients with unresectable disease may receive a second course of treatment in week 7. Patients with localized disease proceed to definitive treatment as determined by the treating physician starting 2-4 weeks after the first injection.
Biological: interleukin-12 gene
Given IT
Other Names:
  • IL-12 gene
  • pIL-12
  • plasmid DNA encoding human interleukin-12
  • plasmid IL-12
Biological: electroporation-mediated plasmid DNA vaccine therapy
Undergo electroporation-mediated plasmid DNA vaccine therapy
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To measure the effect of intratumoral injection of IL-12 plasmid (pIL-12) (interleukin-12 gene) followed by in vivo electroporation (EP) (electroporation-mediated plasmid DNA vaccine therapy) on the local expression of interleukin-12 (IL-12) in the tumor microenvironment in patients with Merkel cell carcinoma (MCC).

SECONDARY OBJECTIVES:

I. To assess the safety of intratumoral pIL-12 injection and in vivo EP in MCC. II. To assess the clinical efficacy of this treatment approach in MCC. III. To assess the immunologic changes resulting from this treatment approach.

OUTLINE:

Patients receive interleukin-12 gene intratumorally (IT) and undergo electrical discharge around the tumor site for electroporation-mediated plasmid DNA vaccine therapy on days 1, 5, and 8. Patients with unresectable disease may receive a second course of treatment in week 7. Patients with localized disease proceed to definitive treatment as determined by the treating physician starting 2-4 weeks after the first injection.

After completion of study treatment, patients are followed up at weeks 4-8 (for patients who received definitive treatment) or 12 (for patients with unresectable disease) and then annually for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have biopsy-confirmed Merkel cell carcinoma
  • Patients must have at least one injectable lesion, defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intratumoral injection and electroporation; the injectable lesion must not be in close proximity to another tissue (e.g. nerve, bone) that could put patient safety at risk
  • Eastern Cooperative Oncology Group (ECOG) performance status score 0 to 2
  • Life expectancy of greater than three months
  • Absolute neutrophil count > 1,000/uL
  • Platelet count > 50,000/uL
  • Creatinine =< 2.0 x upper limit of normal (ULN)
  • Bilirubin =< 2.0 x ULN
  • Prothrombin time (PT) and partial thromboplastin time (PTT) =< 1.5 x ULN
  • Patients must be willing, at the time of the entry to the study, to undergo the pre-treatment fine needle aspiration (FNA) plus biopsy (if indicated) AND the post-treatment FNA plus biopsy (or surgery) of at least one injected lesion (FNA is essential to determine the primary endpoint of the study); NOTE: The pre-treatment biopsy will be obtained from a superficial not-to-be-injected lesion; the post-treatment biopsy of an injected lesion will be obviated if definitive surgical resection is planned
  • The effects of this treatment approach on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document
  • Both men and women, and members of all races and ethnic groups are eligible for this trial

Exclusion Criteria:

  • Patients who have had prior chemotherapy, investigational therapy or a major surgical procedure within 4 weeks or radiotherapy within 2 weeks prior to first day of treatment
  • Patients must not be receiving concurrently any other anti-cancer treatment (including topical agents such as imiquimod) or investigational agents, which could potentially interfere with the study treatment and/or study endpoints
  • Patients with active untreated brain metastases will be excluded
  • Pregnant or breast feeding women are excluded because effects of this treatment on the fetus or passage through milk are unknown
  • Patients with electronic pacemakers or defibrillators or those with a history of life threatening cardiac arrhythmia or uncontrolled seizure disorder are excluded
  • Use of any immunosuppressive treatments including corticosteroids, cyclosporine, mycophenolate mofetil et cetera, within 4 weeks prior to Day 1 of treatment will not be allowed; NOTE: Patients on topical or physiologic doses (for hormone-replacement therapy) of corticosteroids will be allowed
  • Patients, who are judged to be immunosuppressed due to uncontrolled human immunodeficiency virus (HIV) infection, severe uncontrolled diabetes, concurrent hematological malignancy, or other comorbidities, will be excluded
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active serious infection, symptomatic congestive heart failure, unstable angina pectoris, serious autoimmune conditions or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients receiving concurrent therapeutic-dose anticoagulation will be excluded
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01440816

Locations
United States, California
University of California San Francisco Medical Center Recruiting
San Francisco, California, United States, 94143
Contact: Rebecca Bolthouse    415-514-6957    BolthouseR@cc.ucsf.edu   
Contact: Siegrid Yu    415-353-7839      
Principal Investigator: Siegrid Yu         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Nichole Real    206-288-7476    nreal@seattlecca.org   
Contact: Shailender Bhatia    206-288-6765      
Principal Investigator: Shailender Bhatia         
Sponsors and Collaborators
OncoSec Medical Incorporated
Investigators
Principal Investigator: Shailender Bhatia Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: OncoSec Medical Incorporated
ClinicalTrials.gov Identifier: NCT01440816     History of Changes
Other Study ID Numbers: 7248, NCI-2011-01221, P30CA015704
Study First Received: September 23, 2011
Last Updated: March 1, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Merkel Cell
Carcinoma
Carcinoma, Neuroendocrine
Skin Neoplasms
Carcinoma, Basal Cell
Carcinoma, Basosquamous
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Nerve Tissue
Neoplasms by Site
Skin Diseases
Neoplasms, Basal Cell
Neoplasms, Squamous Cell
Interleukin-12
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Adjuvants, Immunologic
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014