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

Uppsala University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Malignant Melanoma

Treatments: Biological: AdCD40L

Study type: Interventional

Funder types: Other

Identifiers

NCT01455259

002:CD40L

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

AdCD40L

Experimental group

Description:

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.

Treatment:

Biological: AdCD40L