NCT01455259

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Sep 2011

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2011

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

October 11, 2011

Completed
8 days until next milestone

First Posted

Study publicly available on registry

October 19, 2011

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

February 17, 2016

Status Verified

February 1, 2016

Enrollment Period

4.3 years

First QC Date

October 11, 2011

Last Update Submit

February 16, 2016

Conditions

Malignant Melanoma

Keywords

AdCD40LAdenoviral vectorCD40LCD154malignant melanoma

Outcome Measures

Primary Outcomes (2)

  • All cause adverse events

    Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.

    during 10 weeks

  • 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

Secondary Outcomes (1)

  • Tumor burden as measured by PET/CT and whole body MR

    At enrollment, week 5 and week 9

Study Arms (1)

AdCD40L

EXPERIMENTAL

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

Interventions

AdCD40LBIOLOGICAL

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.

AdCD40L

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (1)

  • 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.

    PMID: 28427434DERIVED

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasSkin NeoplasmsNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Thomas H Tötterman, MD, PhD

    Uppsala University

    STUDY CHAIR

  • Gustav Ullenhag, MD, PhD

    Uppsala University Hospital

    PRINCIPAL INVESTIGATOR

  • Angelica SI Loskog, PhD

    Uppsala University

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 11, 2011

First Posted

October 19, 2011

Study Start

September 1, 2011

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

February 17, 2016

Record last verified: 2016-02

Locations

SE(1)