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

NCT ID: NCT01455259

Last Updated: 2016-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2016-01-31

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.

Conditions

Malignant Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AdCD40L

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.

Group Type: EXPERIMENTAL

AdCD40L

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Uppsala University Hospital

OTHER

Sponsor Role: collaborator

Uppsala University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas H Tötterman, MD, PhD

Role: STUDY_CHAIR

Uppsala University

Gustav Ullenhag, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University Hospital

Angelica SI Loskog, PhD

Role: STUDY_DIRECTOR

Uppsala University

Locations

Uppsala University Hospital

Uppsala, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 28427434 (View on PubMed)

Other Identifiers

002:CD40L

Identifier Type: -

Identifier Source: org_study_id