Clinical trial NCT01455259: Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors
Official title: Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Malignant Melanoma
Keywords: AdCD40L
Adenoviral vector
CD40L
CD154
malignant melanoma
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: Uppsala University Hospital
First posted: 2011-10-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In this phase I/II trial, immunostimulatory gene therapy (AdCD40L) will be investigated. In Part 1 patients with melanoma will receive AdCD40L as mono therapy. In Part 2A, patients with melanoma and patients with other solid tumors 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Histologically proven diagnosis of malignant solid cancer, ECOG 0-2.
* Disease progression on established treatments or patients not eligible to standard options.
* Signed informed consent must be obtained.

Exclusion Criteria:

* Pregnancy.
* Life expectancy less than 3 months.
* Any significant medical or psychiatric illness that would prevent the patient from giving informed consent or from following the study procedures.
* Patients with severe systemic autoimmune disease.
* Patients that do not consent to that tissue and blood samples are stored in a biobank.

Primary outcomes:
measure: All cause adverse events
timeFrame: during 10 weeks
measure: Immune reactions to adenovirus and spreading of vector
timeFrame: during 10 weeks
Secondary outcomes:
measure: Tumor burden as measured by PET/CT and whole body MR
timeFrame: At enrollment, week 5 and week 9
Other outcomes:
Locations:
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
affiliation: Uppsala University
name: Thomas H Tötterman, MD, PhD
role: STUDY_CHAIR
affiliation: Uppsala University Hospital
name: Gustav Ullenhag, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Uppsala University
name: Angelica SI Loskog, PhD
role: STUDY_DIRECTOR
References:
citation: Schiza A, Wenthe J, Mangsbo S, Eriksson E, Nilsson A, Totterman TH, Loskog A, Ullenhag G. Adenovirus-mediated CD40L gene transfer increases Teffector/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients. J Transl Med. 2017 Apr 20;15(1):79. doi: 10.1186/s12967-017-1182-z.