Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors

Phase 1

Completed

• Conditions: Malignant Melanoma

• Registration Number: NCT01455259
• Lead Sponsor: Uppsala University

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.

Study Timeline

• Study Start: 2011-09
• Study First Submitted: 2011-10-11
• Study First Submitted QC: 2011-10-17
• Study First Posted: 2011-10-19
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2016-02
• Last Update Submitted: 2016-02-16
• Last Update Posted: 2016-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
All cause adverse events	during 10 weeks	Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
Immune reactions to adenovirus and spreading of vector	during 10 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Tumor burden as measured by PET/CT and whole body MR	At enrollment, week 5 and week 9

Trial Locations

Locations (1)

Uppsala University Hospital; 🇸🇪 Uppsala, Sweden