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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01455259
First Posted: October 19, 2011
Last Update Posted: February 17, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Uppsala University Hospital
Information provided by (Responsible Party):
Uppsala University
  Purpose
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.

Condition Intervention Phase
Malignant Melanoma Biological: AdCD40L Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 ]
    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 ]
    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 ]

Enrollment: 30
Study Start Date: September 2011
Study Completion Date: January 2016
Primary Completion Date: January 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.

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01455259


Locations
Sweden
Uppsala University Hospital
Uppsala, Sweden, 75185
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Uppsala University
ClinicalTrials.gov Identifier: NCT01455259     History of Changes
Other Study ID Numbers: 002:CD40L
First Submitted: October 11, 2011
First Posted: October 19, 2011
Last Update Posted: February 17, 2016
Last Verified: February 2016

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