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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Uppsala University
Sponsor:
Collaborator:
Uppsala University Hospital
Information provided by (Responsible Party):
Uppsala University
ClinicalTrials.gov Identifier:
NCT01455259
First received: October 11, 2011
Last updated: March 18, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Disseminated Malignant Melanoma, Advanced Solid Tumors
Biological: AdCD40L
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.

Resource links provided by NLM:


Further study details as provided by Uppsala University:

Primary Outcome Measures:
  • All cause adverse events [ Time Frame: during 10 weeks ] [ Designated as safety issue: Yes ]
    Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.

  • Immune reactions to adenovirus and spreading of vector [ Time Frame: during 10 weeks ] [ Designated as safety issue: Yes ]
    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:
  • Tumor burden as measured by PET/CT and whole body MR [ Time Frame: At enrollment, week 5 and week 9 ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: September 2011
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01455259

Contacts
Contact: Gustav Ullenhag, MD, PhD +46186110000 gustav.ullenhag@akademiska.se
Contact: Aglaia Maleka, MD +46186110000 aglaia.maleka@akademiska.se

Locations
Sweden
Uppsala University Hospital Recruiting
Uppsala, Sweden, 75185
Contact: Gustav Ullenhag, MD, PhD    +46186110000    gustav.ullenhag@akademiska.se   
Contact: Aglaia Maleka, MD    +46186110000    aglaia.maleka@akademiska.se   
Principal Investigator: Gustav Ullenhag, MD, PhD         
Sponsors and Collaborators
Uppsala University
Uppsala University Hospital
Investigators
Study Chair: Thomas H Tötterman, MD, PhD Uppsala University
Principal Investigator: Gustav Ullenhag, MD, PhD Uppsala University Hospital
Study Director: Angelica SI Loskog, PhD Uppsala University
  More Information

No publications provided

Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT01455259     History of Changes
Other Study ID Numbers: 002:CD40L
Study First Received: October 11, 2011
Last Updated: March 18, 2014
Health Authority: Sweden: Medical Products Agency

Keywords provided by Uppsala University:
AdCD40L
Adenoviral vector
CD40L
CD154
malignant melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 28, 2014