Trial of pIL-12 Electroporation Malignant Melanoma (IL12MEL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by OncoSec Medical Incorporated
Sponsor:
Information provided by (Responsible Party):
OncoSec Medical Incorporated
ClinicalTrials.gov Identifier:
NCT01502293
First received: December 21, 2011
Last updated: February 13, 2013
Last verified: February 2013
  Purpose

Study Title: A Multicenter Phase II trial of intratumoral pIL-12 electroporation in advanced stage cutaneous and in transit malignant melanoma

Design: Single-arm, open-label, multicenter Phase II interventional trial

Sample size: 25 evaluable subjects

Sample accrual: 10 per year

Population: Patients with AJCC stage IIIB, IIIC or IV M1a melanoma with cutaneous or in transit lesions accessible to electroporation

Regimen: One 8-day cycle of IL-12 plasmid, 0.5 mg/ml X 1ml intratumorally, with electroporation on days 1, 5, and 8. If there is evidence of persistent disease after 180 days (6 months) and no evidence of systemic progression, patients may be retreated every 3 months at the investigator's discretion. Otherwise, only 1 cycle of treatment will be given.

Objectives: Primary:

• To determine the 24-week distant response rate (complete and partial) of patients with advanced cutaneous melanoma treated with IL-12 plasmid electroporation

Secondary:

  • Local response rate
  • Progression free survival
  • Overall survival
  • Duration of distant response
  • Time to objective response
  • Safety of intratumoral IL-12 in vivo electroporation

Exploratory:

• To describe the immunologic effects of IL-12 plasmid electroporation:

  • Induction of intratumoral IL-12 and IFN-gamma within electroporated melanoma tumors
  • Proportion of tumor-infilitrating lymphocyte subsets such as regulatory (FoxP3+) T cells at baseline and post-treatment
  • Proportion of circulating lymphocyte subsets such as regulatory (FoxP3+) and effector (CD25+CD69+CD4+ and CD25+CD69+CD8+) T cells at baseline and post-treatment
  • Antigen-specific cellular and humoral immune responses in peripheral blood at baseline and post-treatment and whether this is associated with clinical response

Condition Intervention Phase
Melanoma
Biological: Plasmid INTERLEUKIN-12
Device: Intratumoral Electroporation
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Trial of Intratumoral pIL-12 Electroporation in Advanced Stage Cutaneous and in Transit Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by OncoSec Medical Incorporated:

Primary Outcome Measures:
  • Distant response rate [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The distant response rate of patients treated with IL-12 plasmid electroporated in vivo into cutaneous melanoma lesions.


Secondary Outcome Measures:
  • Local response rate and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The local response rate, progression free survival and overall survival of IL-12 plasmid electroporation.

  • Safety and adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    The safety of IL-12 plasmid electroporation as assessed by adverse events.

  • Duration of response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The duration of response and time to objective response.


Estimated Enrollment: 25
Study Start Date: December 2011
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: plasmid Interleukin-12 Biological: Plasmid INTERLEUKIN-12

Each patient will have three treatments applied to two to four lesions; these will be on days 1, 5 and 8. Therefore the maximum plasmid dose injected per patient will be as follows:

Plasmid Concentration = 0.5 mg/mL; Maximum volume that can be injected in one patient on a given day, distributed over 2-4 lesions = 1 mL; Maximum plasmid injected on a given day = 0.5 mg; Maximum plasmid injected in one patient over one cycle = 1.5 mg

Device: Intratumoral Electroporation

Electrical discharge around the tumor site resulting in electroporation of plasmid DNA into tumor cells.

Each patient will have three treatments applied to two to four lesions; these will be on days 1, 5 and 8.


  Eligibility

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

Inclusion Criteria:

  1. Pathologically documented melanoma, AJCC stage IIIB, IIIC or IV M1a with cutaneous melanoma lesions accessible to electroporation. Patients with Stage IIIB or IIIC disease may have cutaneous in-transit disease or cutaneous satellitosis and patients with Stage IV M1a disease may have either of these with distant cutaneous metastatic sites.
  2. Age ≥ 18 years old
  3. ECOG performance status 0-2
  4. Patients may have had prior chemotherapy or immunotherapy (with vaccines or Interferon or IL-2) with progression or persistent disease. All chemotherapy or immunotherapy must be stopped 4 weeks prior to electroporation. Patients may have had radiation therapy, but must have progressive disease after radiation therapy if the lesions to be electroporated are within the radiation field. In addition, it must be at least 2 weeks since administration of radiation therapy and all signs of toxicity must have abated.
  5. Must have a minimum of two eligible tumors and may have up to four eligible tumors treated with electroporation.
  6. Creatinine < 2 x upper limit of normal, and serum bilirubin within institutional normal limits obtained within 4 weeks prior to registration.
  7. Absolute neutrophil count (ANC) > 1000/mm and platelet count > 100,000 /mm within 4 weeks prior to registration.
  8. Able to give informed consent and able to follow guidelines given in the study

Exclusion Criteria:

  1. Prior therapy with IL-12 or prior gene therapy
  2. Concurrent immunotherapy, chemotherapy, or radiation therapy
  3. Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess, etc.) at time of study entry.
  4. Pregnant and breast feeding women are excluded from the study because effects on the fetus are unknown and there may be a risk of increased fetal wastage.
  5. Women of childbearing age must have a negative pregnancy test and be willing to use a highly effective method of contraception. Men who are sexually active must also be willing to use an accepted and effective method of contraception.
  6. Patients with electronic pacemakers or defibrillators are excluded from this study as the effect of electroporation on these devices is unknown.
  7. Life expectancy of less than 6 months
  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: NCT01502293

Locations
United States, California
UCSF Helen Diller Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Rebecca Bolthouse    415-514-6714    bolthouser@cc.ucsf.edu   
Principal Investigator: Adil Daud, MD         
John Wayne Cancer Institute Recruiting
Santa Monica, California, United States, 90404
Contact: MaDonna Johnson    310-582-7438    JohnsonM@JWCI.ORG   
Principal Investigator: Mark B Faries, MD         
United States, Florida
Lakeland Regional Cancer Center Recruiting
Lakeland, Florida, United States, 33805
Contact: Robin S Stewart, RN, PhD    863-904-1877    robin.stewart@lrmc.com   
Principal Investigator: Manuel A Molina, MD         
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   
Principal Investigator: Shailender Bhatia         
Sponsors and Collaborators
OncoSec Medical Incorporated
Investigators
Principal Investigator: Adil Daud, MD University California San Francisco
Study Director: Paul Goldfarb, M.D. OncoSec Medical Incorporated
  More Information

No publications provided

Responsible Party: OncoSec Medical Incorporated
ClinicalTrials.gov Identifier: NCT01502293     History of Changes
Other Study ID Numbers: 11854
Study First Received: December 21, 2011
Last Updated: February 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
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