Uveal MelanomaPhase 1/2NCT00929019
Messenger Ribonucleic Acid (mRNA) Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
A Phase 1/2 study testing autologous dendritic cells electroporated with mRNA in people with Uveal Melanoma, run by Radboud University Medical Center at 2 sites in Netherlands.
Trial summary
1. Rationale Immunotherapy applying ex vivo generated and tumor antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- autologous dendritic cells electroporated with mRNA
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 2 sitesNetherlands
- Study dates
- Jun 2009to Apr 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histological documented uveal melanoma
- HLA-A2.1 phenotype (intervention arm)
- non-HLA-A2.1 phenotype (control arm)
- melanoma expressing gp100 and/or tyrosinase
- high risk genetic profile (loss of chromosome 3) determined by FISH
- interval since local treatment of uveal melanoma < 12 months
Show all 15Show fewer
- no signs of liver metastasis determined by diagnostic CT-abdomen
- normal serum LDH
- no signs of cerebral metastases
- bilirubin < 25 micromol/l
- WHO performance scale 0-1
- age 18-75 years
- written informed consent
- expected adequacy of followup
- no pregnant or lactating women
Who cannot join
- history of second malignancy, except adequately treated basal cell carcinoma
- serious active infections
- autoimmune disease or organ allografts
- concomitant use of immunosuppressive drugs
- known allergy to shell-fish
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, 6500HB
The Rotterdam Eye Hospital
Rotterdam, South Holland, 3000LM
About this study
Official title: mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
- Rationale Immunotherapy applying ex vivo generated and tumor antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Most of the successful results have been observed in patients with minimal residual disease, rather than patients with advanced metastatic disease. Moreover, the investigators' preliminary results show that presence of tumor epitope specific T cells in biopsies taken from delayed type hypersensitivity (DTH) reaction sites highly correlates with prolonged progression free survival (PFS). Within uveal melanoma patients, a group with high risk of metastatic disease can be identified on basis of tumor specific genetic changes in loss of chromosome 3. At present no standard adjuvant or systemic treatment is available. Applying DC-based immunotherapy in this group of high risk patients might reduce the risk of recurrence without interference in the current treatment guidelines.
- Objectives In this joint clinical study of Radboud University Nijmegen Medical Centre (RUNMC) and Rotterdam Eye Hospital, the investigators aim to determine the in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC.
- Study design This study is an open label non-randomized phase II intervention study.
- Study population The investigators' study population consists of HLA-A2 positive patients with a high risk uveal melanoma with proven expression of melanoma associated antigens tyrosinase and/or gp100.
- Main study endpoints
This is an exploratory study aiming to demonstrate proof of principle. The first study endpoints are in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC, administered i.v./i.d. and toxicity. Secondary study endpoints are progression free survival, overall survival, and toxicity.
- Conditions
- Uveal Melanoma
- Being tested
- autologous dendritic cells electroporated with mRNA
- Keywords
- uveal melanoma, chromosome 3, high risk, immunotherapy, adjuvant, high risk genetic profile, loss of chromosome 3
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous dendritic cells electroporated with mRNABiological
Autologous mature monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase are vaccinated intradermal/intravenously 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations.
| Study group | Role | What they receive |
|---|---|---|
| dendritic cell vaccination | Experimental | HLA-A2.1 positive patient will receive 3 biweekly intradermal/intravenous vaccination with autologous mRNA transfected mature dendritic cells, followed by a DTH skin test for monitoring purposes. One such cycle is repeated every 6 months if no signs of progression, up to a total of 3 cycles. Receives: Biological: autologous dendritic cells electroporated with mRNA |
| control arm | No intervention | For comparison, HLA-A2.1 negative patients will be monitored for clinical response (secondary endpoint). |
What is being measured
The primary outcome is the main question the study is designed to answer.
immunological response
Measured: 2 years
Secondary outcomes (1)
clinical response (progression free survival)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2009 (estimated)
- Study startJun 2009
- Primary completionApr 2016
- Study completionApr 2016
Why it stopped: slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Rotterdam Eye Hospital
- Responsible party
- Sponsor
- Investigators
- Cornelis JA Punt, prof.MD, Principal investigator, Radboud University Nijmegen Medical Centre, Dept of Medical Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00929019
- Sponsor's protocol ID
- NL22553.000.08
- Other IDs
- KUN2008-035
- Status last verified
- Sep 2015
- First submitted
- 25 Jun 2009
- Last updated
- 7 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- mRNA Transfected Dendritic Cell Vaccination in High Risk Uveal Melanoma Patients
- ClinicalTrials.gov ID
- NCT00929019
- Acronym / sponsor ID
- NL22553.000.08
- Conditions
- Uveal Melanoma
- Keywords
- uveal melanoma, chromosome 3, high risk, immunotherapy, adjuvant, high risk genetic profile, loss of chromosome 3
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: slow accrual
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Rotterdam Eye Hospital
- Study start
- Jun 2009
- Primary completion
- Apr 2016 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 26 Jun 2009 (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.
- Rationale Immunotherapy applying ex vivo generated and tumor antigen-loaded dendritic cells (DC) has now successfully been introduced in the clinic. A limited, but consistent, number of objective immunological and clinical responses have been observed. Most of the successful results have been observed in patients with minimal residual disease, rather than patients with advanced metastatic disease. Moreover, the investigators' preliminary results show that presence of tumor epitope specific T cells in biopsies taken from delayed type hypersensitivity (DTH) reaction sites highly correlates with prolonged progression free survival (PFS). Within uveal melanoma patients, a group with high risk of metastatic disease can be identified on basis of tumor specific genetic changes in loss of chromosome 3. At present no standard adjuvant or systemic treatment is available. Applying DC-based immunotherapy in this group of high risk patients might reduce the risk of recurrence without interference in the current treatment guidelines.
- Objectives In this joint clinical study of Radboud University Nijmegen Medical Centre (RUNMC) and Rotterdam Eye Hospital, the investigators aim to determine the in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC.
- Study design This study is an open label non-randomized phase II intervention study.
- Study population The investigators' study population consists of HLA-A2 positive patients with a high risk uveal melanoma with proven expression of melanoma associated antigens tyrosinase and/or gp100.
- Main study endpoints
This is an exploratory study aiming to demonstrate proof of principle. The first study endpoints are in vivo immunological response induced in high risk uveal melanoma patients vaccinated with mRNA-transfected DC, administered i.v./i.d. and toxicity. Secondary study endpoints are progression free survival, overall survival, and toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| dendritic cell vaccination | Experimental | Biological: autologous dendritic cells electroporated with mRNAHLA-A2.1 positive patient will receive 3 biweekly intradermal/intravenous vaccination with autologous mRNA transfected mature dendritic cells, followed by a DTH skin test for monitoring purposes. One such cycle is repeated every 6 months if no signs of progression, up to a total of 3 cycles. |
| control arm | No intervention | –For comparison, HLA-A2.1 negative patients will be monitored for clinical response (secondary endpoint). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- histological documented uveal melanoma
- HLA-A2.1 phenotype (intervention arm)
- non-HLA-A2.1 phenotype (control arm)
- melanoma expressing gp100 and/or tyrosinase
- high risk genetic profile (loss of chromosome 3) determined by FISH
Key exclusion criteria (5 listed)
- history of second malignancy, except adequately treated basal cell carcinoma
- serious active infections
- autoimmune disease or organ allografts
- concomitant use of immunosuppressive drugs
- known allergy to shell-fish
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 |
|---|---|---|
| autologous dendritic cells electroporated with mRNAAutologous mature monocyte-derived dendritic cells electroporated with mRNA encoding gp100 and tyrosinase are vaccinated intradermal/intravenously 3 times with biweekly intervals every 6 months, if no signs of progression, for a total of 9 vaccinations. | Biological | dendritic cell vaccination |
Primary outcome
immunological response
Time frame: 2 years
1 secondary outcome
clinical response (progression free survival)
Time frame: 5 years
Results and safety
The study was stopped early (reason given: slow accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2018.
- Radboud University Nijmegen Medical CentreLink provided by the sponsor.
- Rotterdam Eye HospitalLink provided by the sponsor.
- Nijmegen Centre for Molecular Life SciencesLink provided by the sponsor.
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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.
Cornelis JA Punt, prof.MD principal investigator
Radboud University Nijmegen Medical Centre, Dept of Medical Oncology
2 sites 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 autologous dendritic cells electroporated with mRNA in people with Uveal Melanoma, run by Radboud University Medical Center at 2 sites in Netherlands.
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 15 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: stopped early, as of the sponsor's last update on 7 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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 was stopped early (reason given: slow accrual). Results are not available in the source record.
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?
immunological response (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Dec 2018.