Isolated Limb Infusion Chemotherapy With Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma
This phase I/II trial studies the safety, best dose and effectiveness of targeted gene therapy combined with isolated limb infusion (ILI) of melphalan and dactinomycin for treating patients with advanced extremity melanoma that cannot be removed by surgery. Adding gene therapy to a standard chemotherapy regimen in the isolated limb may enhance anti-cancer effects by inducing a systemic immune response against the tumor cells.
Biological: Conditionally replicative adenovirus 3/5-delta
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of Isolated Limb Infusion and Targeted Gene Therapy for Advanced, Unresectable Extremity Melanoma|
- Optimal tolerated dose (OTD) of CRAd 3/5 [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]Defined as the dose level at which > 50% of target lesion viral infectivity is achieved and < 2 of 6 patients have dose limiting toxicities.
- Response rate (complete response [CR] + partial response [PR]) of CRAd 3/5-delta in combination with standard M-ILI (Phase II) [ Time Frame: 3 months ] [ Designated as safety issue: No ]Assessed using revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
- Progression Free Survival (Phase II) [ Time Frame: 2 years ] [ Designated as safety issue: No ]Duration of time from start of treatment to time of progression or death, whichever occurs first.
- Safety of CRAd 3/5-delta in combination with standard M-ILI [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
- Infectivity rate of CRAd 3/5-delta [ Time Frame: 2 days; baseline and day 1 or 2 post treatment ] [ Designated as safety issue: No ]Lesion biopsies; quantified using immunohistochemical staining method.
|Study Start Date:||December 2014|
|Estimated Study Completion Date:||February 2016|
|Estimated Primary Completion Date:||February 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (targeted gene therapy and ILI)
Patients receive melphalan and dactinomycin via ILI. Patients then receive CRAd 3/5-delta via ILI.
Given via ILI
Other Name: ACT-D, actinomycin C1, actinomycin D, AD, Cosmegen, DACTDrug: melphalan
Given via ILI
Other Name: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin, MelfalanBiological: Conditionally replicative adenovirus 3/5-delta
Given via ILI
Other Name: CRAd 3/5-delta
Please refer to this study by its ClinicalTrials.gov identifier: NCT01531244
|Principal Investigator:||Ryan Fields, M.D.||Washington University School of Medicine|