Malignant MelanomaPhase 1/2NCT01455259
Phase I/IIa AdCD40L Immunogene Therapy for Malignant Melanoma and Other Solid Tumors
A Phase 1/2 study testing AdCD40L in people with Malignant Melanoma, run by Uppsala University at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- AdCD40L
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteSweden
- Study dates
- Sep 2011to Jan 2016
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
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.
Read the 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
- Being tested
- AdCD40L
- Keywords
- AdCD40L, Adenoviral vector, CD40L, CD154, malignant melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: AdCD40L |
What is being measured
The primary outcome is the main question the study is designed to answer.
All cause adverse events
Adverse events will be documented such as inflammation, fever, pain, changes in blood pressure, pulse etc.
Measured: 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).
Measured: during 10 weeks
Secondary outcomes (1)
Tumor burden as measured by PET/CT and whole body MR
Measured: At enrollment, week 5 and week 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2011 (estimated)
- Study startSep 2011
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Uppsala UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Uppsala University
- Sponsor type
- University, hospital or other
- Collaborators
- Uppsala University Hospital
- Responsible party
- Sponsor
- Investigators
- Thomas H Tötterman, MD, PhD, Study chair, Uppsala UniversityGustav Ullenhag, MD, PhD, Principal investigator, Uppsala University HospitalAngelica SI Loskog, PhD, Study director, Uppsala University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01455259
- Sponsor's protocol ID
- 002:CD40L
- Status last verified
- Feb 2016
- First submitted
- 11 Oct 2011
- Last updated
- 17 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28427434
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/IIa AdCD40L Immunogene Therapy for Patients With Advanced Malignant Disease.
- ClinicalTrials.gov ID
- NCT01455259
- Acronym / sponsor ID
- 002:CD40L
- Conditions
- Malignant Melanoma
- Keywords
- AdCD40L, Adenoviral vector, CD40L, CD154, malignant melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Uppsala UniversityUniversity, hospital or other
- Collaborators
- Uppsala University Hospital
- Study start
- Sep 2011
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 19 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AdCD40L | Experimental | Biological: AdCD40LTreatments 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdCD40LAdenoviral 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. | Biological | AdCD40L |
Primary outcome
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).
1 secondary outcome
Tumor burden as measured by PET/CT and whole body MR
Time frame: At enrollment, week 5 and week 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2016.
- Derived from this study: PubMed 28427434Schiza 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas H Tötterman, MD, PhD study chair
Uppsala University
Gustav Ullenhag, MD, PhD principal investigator
Uppsala University Hospital
Angelica SI Loskog, PhD study director
Uppsala University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AdCD40L in people with Malignant Melanoma, run by Uppsala University at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All cause adverse events (time frame: during 10 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01455259, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2016.