Safety Study of Adenovirus Vector Engineered to Express hIL-12 (Human Interleukin 12) in Combination With Activator Ligand to Treat Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Ziopharm
Sponsor:
Information provided by (Responsible Party):
Ziopharm
ClinicalTrials.gov Identifier:
NCT01397708
First received: July 14, 2011
Last updated: March 11, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Unresectable Stage III or IV Melanoma
Biological: INXN-2001
Drug: INXN-1001
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
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

Resource links provided by NLM:


Further study details as provided by Ziopharm:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Inform the selection of an INXN-1001 dose(s) for further study in combination with INXN-2001. [ Time Frame: June 2014 ] [ Designated as safety issue: No ]
  • To obtain preliminary anti-tumor activity according to RECIST 1.1 criteria. [ Time Frame: June 2014 ] [ Designated as safety issue: No ]
  • Evaluate the immunological effect of study treatment in terms of cellular and tumoral immune responses. [ Time Frame: June 2014 ] [ Designated as safety issue: No ]
  • Evaluate the extent of the uptake of INXN-2001 into tumor cells and tumor-infiltrating immune cells. [ Time Frame: June 2014 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: August 2011
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).
Biological: INXN-2001
  • approximately 1.0 x 1012 viral particles (vp) per injection
  • one intratumoral injection of INXN-2001 per study cycle
  • maximum of 6 study cycles
Other Name: Ad-RTS-hIL-12
Drug: INXN-1001
  • 4 dose cohorts (5mg/day, 20mg/day, 100mg/day, and 160mg/day)
  • 7 oral daily doses of INXN-1001 per study cycle
  • maximum of 6 study cycles
  • 1 Expansion cohort at a single dose level at or below MTD (160mg/day)
Other Name: Activator Ligand

Detailed Description:

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.
  Eligibility

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

Inclusion Criteria:

  • Males or females of all races ≥ 18 years of age, who have provided written informed consent prior to completing any study specific procedure.
  • Unresectable Stage III or Stage IV melanoma arising from any site other than ocular melanoma.
  • A minimum of 2 accessible nonvisceral lesions (shortest diameter ≥1 cm) or palpable tumor-involved lymph nodes (shortest diameter ≥1.5 cm).
  • ECOG performance status of 0 or 1 (Appendix 1).
  • Adequate bone marrow, liver, and renal function.
  • An expected survival of at least approximately 6 months.
  • Male and female subjects must agree to use a highly reliable method of birth control (expected failure rate less than 5% per year) from the screening visit through 28 days after the last dose of study drug.

Exclusion Criteria:

  • Any prior anti-cancer therapy or investigational agent within 28 days prior to the first dose of study drug. (NOTE: For the expansion cohort ONLY, if subjects received ipilimumab, a 90-day washout period since last dose of ipilimumab is required. If subjects received other immunomodulating therapies (eg, anti-PD1 antibodies), the medical monitor should be contacted and an evaluation will be made.)
  • Clinically significant infection requiring systemic antibacterial, antifungal, or antiviral therapy within 2 weeks of the first dose of study drug.
  • History of HIV infection.
  • Active autoimmune disease requiring steroids (>10 mg prednisone or comparable) or other immunosuppressive therapy (e.g., methotrexate, etc.).
  • Documented symptomatic brain metastases. Screening for brain lesions by CT or MRI is not required for all potential subjects; however, if there are any neurological signs or symptoms consistent with brain metastases, then a brain CT or MRI should be performed as clinically indicated.
  • Any medications that induce, inhibit or are substrates of CYP450 3A4 within 7 days prior to the first dose of study drug.
  • Prior history of hematopoietic stem cell transplant or organ allograft.
  • Other concurrent clinically active malignant disease, with the exception of other cancers of the skin.
  • Females who are nursing or pregnant.
  • Subjects who have a history of hypersensitivity that may relate to any component of the study drugs, e.g. to benzoic acid since INXN-1001 contains two benzene rings.
  • Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a subject and/or their compliance with the protocol.
  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: NCT01397708

Contacts
Contact: Rachael Murphy 617-778-1081 rmurphy@ziopharm.com
Contact: Gina Weber 617-778-2262 gweber@ziopharm.com

Locations
United States, California
Recruiting
Santa Monica, California, United States, 90404
United States, Illinois
Active, not recruiting
Park Ridge, Illinois, United States, 60068
United States, Indiana
Recruiting
Goshen, Indiana, United States, 46526
Recruiting
Indianapolis, Indiana, United States, 46202
United States, Kentucky
Recruiting
Louisville, Kentucky, United States, 40202
United States, Missouri
Recruiting
St. Louis, Missouri, United States, 63110
United States, New Jersey
Recruiting
Morristown, New Jersey, United States, 07960
United States, Pennsylvania
Withdrawn
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
Recruiting
Dallas, Texas, United States, 75201
United States, Vermont
Recruiting
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Ziopharm
  More Information

No publications provided

Responsible Party: Ziopharm
ClinicalTrials.gov Identifier: NCT01397708     History of Changes
Other Study ID Numbers: ADA1001, ATI001-101
Study First Received: July 14, 2011
Last Updated: March 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Ziopharm:
Melanoma
Unresectable

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

ClinicalTrials.gov processed this record on August 21, 2014