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

Malignant Melanoma Clinical Trial

Official title:

Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01455259
• Other study ID #: 002:CD40L
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 11, 2011
• Last updated: February 16, 2016
• Start date: September 2011
• Est. completion date: January 2016

Study information

• Verified date: February 2016
• Source: Uppsala University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malignant Melanoma
• Melanoma

Intervention

Biological:
• AdCD40L
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.

Locations

Country	Name	City	State
Sweden	Uppsala University Hospital	Uppsala

Sponsors (2)

Lead Sponsor	Collaborator
Uppsala University	Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All cause adverse events	Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.	during 10 weeks	Yes
Primary	Immune reactions to adenovirus and spreading of vector	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).	during 10 weeks	Yes
Secondary	Tumor burden as measured by PET/CT and whole body MR		At enrollment, week 5 and week 9	No