Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.|
- All cause adverse events [ Time Frame: during 10 weeks ] [ Designated as safety issue: Yes ]Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
- Immune reactions to adenovirus and spreading of vector [ Time Frame: during 10 weeks ] [ Designated as safety issue: Yes ]Immune reactions to adenovirus will be measured by evaluating the increase of anti-adenoviral antibodies in the patients at different time points using an ELISA. Spreading of vector will be evaluated by real time PCR to detect adenovirus vector copies in blood (plasma and erythrocyte fraction).
- Tumor burden as measured by PET/CT and whole body MR [ Time Frame: At enrollment, week 5 and week 9 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2011|
|Study Completion Date:||January 2016|
|Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Treatments once a week with 2.5x10e11 VP AdCD40L, maximum 4 treatments (total dose 1x10e12 VP). If no effect in less than 2 out of 6 melanoma patients, the following 9 melanoma patients and 6 patients with other solid tumors will receive preconditioning therapy 1-2 days prior to first and last treatment with 300mg/m2 cyclophosphamid. The next 9 melanoma patients will receive one local radiotherapy.
Adenoviral serotype 5 vector, E1/E3 deleted. Human CD40L gene insert driven by RSV promoter. Vector diluted in infusion solution, 500uL solution containing 2.5x10e11 VP is intratumorally injected/treatment.
In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma (n=6) will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma (n=9) and patients with other solid tumors (n=6) will receive AdCD40L in combination with low dose cyclophosphamide. In Part 2B, patients with melanoma will receive AdCD40L in combination with one local radiotherapy and cyclophosphamide. AdCD40L is given by weekly injections of 2.5x10e11 VP, 4x; total dose 1x10e12 VP. A maximum of 30 patients will be included in this trial.
AdCD40L is an adenoviral nonreplicating vector carrying the human CD40L gene. AdCD40L infects tumor cells upon intratumoral injection and deliver the CD40L gene into the cells whereupon the virus is destroyed. CD40L is then expressed as a membrane-bound protein and interacts with the CD40 receptor expressed by for example dendritic cells (DCs) in the tumor area. DCs mature upon CD40/CD40L interactions and activates tumor-specific T cell responses.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01455259
|Uppsala University Hospital|
|Uppsala, Sweden, 75185|
|Study Chair:||Thomas H Tötterman, MD, PhD||Uppsala University|
|Principal Investigator:||Gustav Ullenhag, MD, PhD||Uppsala University Hospital|
|Study Director:||Angelica SI Loskog, PhD||Uppsala University|