Safety Study of Adenovirus Vector Engineered to Express hIL-12 in Combination With Activator Ligand to Treat Melanoma
This research study involves two investigational drugs, an Activator Ligand (INXN-1001) in combination with an Adenovirus Vector Engineered to Express hIL-12 (INXN-2001). IL-12 is a protein that may improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.
The main purpose of this study is to evaluate the safety and tolerability of tumor injections of INXN-2001 given in combination with different doses of INXN-1001.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II, Open Label Study of Ad-RTS-hIL-12, an Adenovirus Vector Engineered to Express hIL-12, in Combination With an Oral Activator Ligand, in Subjects With Unresectable Stage III or IV Melanoma|
- Evaluate the safety and tolerability of intratumoral injections of INXN-2001 (Ad-RTS-hIL-12) at a constant dose in combination with inter-cohort escalating doses of INXN-1001 (activator ligand) in subjects with unresectable Stage III or IV melanoma. [ Time Frame: June 2014 ]Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs). Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.
- Inform the selection of an INXN-1001 dose(s) for further study in combination with INXN-2001. [ Time Frame: June 2014 ]
- To obtain preliminary anti-tumor activity according to RECIST 1.1 criteria. [ Time Frame: June 2014 ]
- Evaluate the immunological effect of study treatment in terms of cellular and tumoral immune responses. [ Time Frame: June 2014 ]
- Evaluate the extent of the uptake of INXN-2001 into tumor cells and tumor-infiltrating immune cells. [ Time Frame: June 2014 ]
|Study Start Date:||August 2011|
|Study Completion Date:||September 2014|
|Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
Experimental: INXN-1001 in combination with INXN-2001
Intratumoral injections of INXN-2001 (Ad-RTS-hIL-12) at a constant dose in combination with inter-cohort escalating doses of INXN-1001 (activator ligand).
Other Name: Ad-RTS-hIL-12Drug: INXN-1001
Other Name: Activator Ligand
Single-arm, open label, Phase I/II dose escalation study of intratumoral injections INXN-2001 and oral INXN-1001 in subjects with unresectable Stage III or IV melanoma.
Four sequential dose escalation cohorts of INXN-1001 in combination with a fixed dose of INXN-2001 are planned. Subject enrollment and dose escalation will proceed according to a standard 3+3 design.
Approximately 15 additional subjects will be enrolled as an expansion cohort at a single dose level at or below the MTD.
- Safety and tolerability will be assessed by the incidence and severity of adverse events.
- The antitumor activity of study treatment will be assessed according to RECIST v1.1 guidelines. Additional assessment of anti-tumor activity will be explored based on total measurable tumor burden.
- Immunological and biological markers of response will include examinations of tumor biopsy samples, cytokine levels, peripheral blood mononuclear cells (PBMC) and antibody response to INXN-2001.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01397708
|United States, California|
|The Angeles Clinic|
|Los Angeles, California, United States, 90404|
|United States, Illinois|
|Park Ridge, Illinois, United States, 60068|
|United States, Indiana|
|Indiana University Health Goshen Center for Cancer Care|
|Goshen, Indiana, United States, 46526|
|United States, Kentucky|
|James Graham Brown Cancer Center|
|Louisville, Kentucky, United States, 40202|
|United States, Missouri|
|St. Louis, Missouri, United States, 63110|
|United States, New Jersey|
|Atlantic Melanoma Center|
|Morristown, New Jersey, United States, 07960|
|United States, Pennsylvania|
|Easton, Pennsylvania, United States, 15232|
|United States, Texas|
|Mary Crowley Cancer Research Center|
|Dallas, Texas, United States, 75201|
|United States, Vermont|
|Fletcher Allen Health|
|Burlington, Vermont, United States, 05401|
|Study Director:||Francois Lebel, MD||ZIOPHARM Oncology|