Cutaneous MelanomaPhase 1NCT04274816
Intradermal Injection of Anti-CTLA-4 in Patients With Stage I/II Melanoma
A Phase 1 study testing Tremelimumab in people with Cutaneous Melanoma, run by A.J.M. van den Eertwegh.
Trial summary
This study evaluates the clinical safety and tolerability, and the immunological effects of local intradermal injection of tremelimumab in patients with clinical stage I/II melanoma patients undergoing a sentinel node biopsy (SNB). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Melanoma
- What is being tested?
- Tremelimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- No sites listed yet
- Study dates
- 10 Jul 2012to 27 Feb 2014
- Phase
- Phase 1
- 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
- Age ≥ 18 years
- Clinical stage I/II melanoma patients, planned to undergo a sentinel lymph node biopsy (SNB)
- ECOG performance status 0 or 1
- White blood count (WBC) ≥ 3 x10^9/L
- Platelet count ≥ 100 x10^9/L
- Hemoglobin ≥ 6.5 mmol/L
- Serum creatinine ≤ 2.5 x ULN
- Total serum bilirubin, AST, ALT and LDH ≤ 2x ULN
Who cannot join
- Non-oncology vaccine therapy used for prevention of infectious diseases (up-to) 4 weeks prior and/r 8 weeks after any dose of tremelimumab
- Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist
- Uncontrolled infectious disease including negative testing for HIV, HBV, HCV
- Autoimmune disease
About this study
Official title: Releasing the Brakes on CD8+ T Cells in the Melanoma Sentinel Lymph Node by Pre-operative Local Administration of Low-dose Anti-CTLA-4 (Tremelimumab)
This study evaluates the clinical safety and tolerability, and the immunological effects of local intradermal injection of tremelimumab in patients with clinical stage I/II melanoma patients undergoing a sentinel node biopsy (SNB). Patients will be treated by local intradermal injections around the excision site of the primary tumor with escalating doses of 2, 5, 10 or 20 mg tremelimumab.
Read the detailed description
Although of limited therapeutic value, the SLN procedure has proven a useful prognostic tool for the assessment of melanoma relapse and mortality risk. Moreover, the SLN is of great value for the assessment of immunological interventions for melanoma. Since early melanoma development is accompanied by impaired immune effector functions primarily in the SLN, there is a strong rationale for therapeutic immune modulation of the SLN aimed at strengthening cellular immune functions.
The investigator now propose a phase I dose escalation study to administer intradermally a single clinical dose of tremelimumab/anti-CTLA-4 locally at the primary tumor excision site of patients with clinical stage I/II melanoma. Such a single local administration aimed at conditioning of the SLN should allow for the use of relatively low anti-CTLA-4 dosages without excess risk of autoimmune effects.
- Conditions
- Cutaneous Melanoma
- Being tested
- Tremelimumab
- Keywords
- Stage I-II melanoma, Anti-CTLA-4, Immunotherapy, Neoadjuvant
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TremelimumabDrug
Also called Anti-CTLA-4
Intradermal injection of tremelimumab 7 days prior to sentinel node biopsy, with escalating doses of 2, 5, 10 or 20 mg tremelimumab (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients).
| Study group | Role | What they receive |
|---|---|---|
| Tremelimumab | Experimental | Intradermal injection of tremelimumab at the primary melanoma excision site, 7 days prior to sentinel node biopsy (SNB), with escalating doses of 2, 5, 10 or 20 mg tremelimumab (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients). Receives: Drug: Tremelimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as assessed by CTCAE V3.0
The descriptions and grading scales of CTCAE V 3.0 will be utilized for all toxicity reporting
Measured: From the time of injection until 28 days after injection of tremelimumab
Change in frequency of immune cell populations (compared to baseline) assessed by immune monitoring through flow cytometry,
Blood samples and sentinel lymph node material will be collected and then analyzed by flow cytometry. Changes in frequency of tumor-specific T-cells, Tregs and dendritic subsets will be assesess and compared to baseline (time of the injection of the intradermal injection)
Measured: 7 days after the intradermal injection of tremelimumab
Change in activation status of immune cell populations (compared to baseline) assessed by immune monitoring through flow cytometry,
Blood samples and sentinel lymph node material will be collected and then analyzed by flow cytometry. Changes in expression level of surface antigens for tumor-specific T-cells, Tregs and dendritic subsets are analyzed and compared to baseline (time of injection of tremelimumab)
Measured: 7 days after the intradermal injection of tremelimumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2020
- Study start10 Jul 2012
- Primary completion27 Feb 2014
- Study completion27 Feb 2014
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 Cutaneous MelanomaStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Seven days before undergoing a SNB, clinical stage I/II melanoma patients will be treated with an intradermal injection of tremelimumab, around the excision site of the primary tumor. Escalating doses of 2, 5, 10, or 20 mg of tremelimumab will be given (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients).
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- A.J.M. van den Eertwegh
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, A.J.M. van den Eertwegh, Amsterdam UMC, location VUmc
- Investigators
- Tanja D de Gruijl, Principal investigator, Amsterdam UMC, location VUmcAlfons JM van den Eertwegh, Principal investigator, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04274816
- Sponsor's protocol ID
- 2011-000139-10
- Status last verified
- Feb 2020
- First submitted
- 6 Feb 2020
- Last updated
- 18 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
van Pul KM, Notohardjo JCL, Fransen MF, Koster BD, Stam AGM, Chondronasiou D, Lougheed SM, Bakker J, Kandiah V, van den Tol MP, Jooss K, Vuylsteke RJCLM, van den Eertwegh AJM, de Gruijl TD. Local delivery of low-dose anti-CTLA-4 to the melanoma lymphatic basin leads to systemic Treg reduction and effector T cell activation. Sci Immunol. 2022 Jul 15;7(73):eabn8097. doi: 10.1126/sciimmunol.abn8097. Epub 2022 Jul 15.
PubMed 35857579
Study at a glance
From the registry record, last updated by the sponsor on 18 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Releasing the Brakes on CD8+ T Cells in the Melanoma Sentinel Lymph Node by Pre-operative Local Administration of Low-dose Anti-CTLA-4 (Tremelimumab)
- ClinicalTrials.gov ID
- NCT04274816
- Acronym / sponsor ID
- 2011-000139-10
- Conditions
- Cutaneous Melanoma
- Keywords
- Stage I-II melanoma, Anti-CTLA-4, Immunotherapy, Neoadjuvant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- A.J.M. van den EertweghUniversity, hospital or other
- Study start
- 10 Jul 2012 (actual)
- Primary completion
- 27 Feb 2014 (actual)
- Study completion
- 27 Feb 2014 (actual)
- First posted
- 18 Feb 2020 (actual)
- 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.
This study evaluates the clinical safety and tolerability, and the immunological effects of local intradermal injection of tremelimumab in patients with clinical stage I/II melanoma patients undergoing a sentinel node biopsy (SNB). Patients will be treated by local intradermal injections around the excision site of the primary tumor with escalating doses of 2, 5, 10 or 20 mg tremelimumab.
Detailed description
Although of limited therapeutic value, the SLN procedure has proven a useful prognostic tool for the assessment of melanoma relapse and mortality risk. Moreover, the SLN is of great value for the assessment of immunological interventions for melanoma. Since early melanoma development is accompanied by impaired immune effector functions primarily in the SLN, there is a strong rationale for therapeutic immune modulation of the SLN aimed at strengthening cellular immune functions.
The investigator now propose a phase I dose escalation study to administer intradermally a single clinical dose of tremelimumab/anti-CTLA-4 locally at the primary tumor excision site of patients with clinical stage I/II melanoma. Such a single local administration aimed at conditioning of the SLN should allow for the use of relatively low anti-CTLA-4 dosages without excess risk of autoimmune effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Seven days before undergoing a SNB, clinical stage I/II melanoma patients will be treated with an intradermal injection of tremelimumab, around the excision site of the primary tumor. Escalating doses of 2, 5, 10, or 20 mg of tremelimumab will be given (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients).
| Arm | Type | Receives |
|---|---|---|
| Tremelimumab | Experimental | Drug: TremelimumabIntradermal injection of tremelimumab at the primary melanoma excision site, 7 days prior to sentinel node biopsy (SNB), with escalating doses of 2, 5, 10 or 20 mg tremelimumab (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥ 18 years
- Clinical stage I/II melanoma patients, planned to undergo a sentinel lymph node biopsy (SNB)
- ECOG performance status 0 or 1
- White blood count (WBC) ≥ 3 x10^9/L
- Platelet count ≥ 100 x10^9/L
Key exclusion criteria (4 listed)
- Non-oncology vaccine therapy used for prevention of infectious diseases (up-to) 4 weeks prior and/r 8 weeks after any dose of tremelimumab
- Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist
- Uncontrolled infectious disease including negative testing for HIV, HBV, HCV
- Autoimmune disease
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 |
|---|---|---|
| TremelimumabAlso: Anti-CTLA-4Intradermal injection of tremelimumab 7 days prior to sentinel node biopsy, with escalating doses of 2, 5, 10 or 20 mg tremelimumab (3 patients per dose level with an expansion at the optimal dose level with an additional 5 patients). | Drug | Tremelimumab |
Primary outcome
Number of participants with adverse events as assessed by CTCAE V3.0
Time frame: From the time of injection until 28 days after injection of tremelimumab
The descriptions and grading scales of CTCAE V 3.0 will be utilized for all toxicity reporting
Change in frequency of immune cell populations (compared to baseline) assessed by immune monitoring through flow cytometry,
Time frame: 7 days after the intradermal injection of tremelimumab
Blood samples and sentinel lymph node material will be collected and then analyzed by flow cytometry. Changes in frequency of tumor-specific T-cells, Tregs and dendritic subsets will be assesess and compared to baseline (time of the injection of the intradermal injection)
Change in activation status of immune cell populations (compared to baseline) assessed by immune monitoring through flow cytometry,
Time frame: 7 days after the intradermal injection of tremelimumab
Blood samples and sentinel lymph node material will be collected and then analyzed by flow cytometry. Changes in expression level of surface antigens for tumor-specific T-cells, Tregs and dendritic subsets are analyzed and compared to baseline (time of injection of tremelimumab)
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 18 Feb 2020.
- Derived from this study: PubMed 35857579van Pul KM, Notohardjo JCL, Fransen MF, Koster BD, Stam AGM, Chondronasiou D, Lougheed SM, Bakker J, Kandiah V, van den Tol MP, Jooss K, Vuylsteke RJCLM, van den Eertwegh AJM, de Gruijl TD. Local delivery of low-dose anti-CTLA-4 to the melanoma lymphatic basin leads to systemic Treg reduction and effector T cell activation. Sci Immunol. 2022 Jul 15;7(73):eabn8097. doi: 10.1126/sciimmunol.abn8097. Epub 2022 Jul 15.
- Individual participant dataSharing planned: No
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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.
Tanja D de Gruijl principal investigator
Amsterdam UMC, location VUmc
Alfons JM van den Eertwegh principal investigator
Amsterdam UMC, location VUmc
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tremelimumab in people with Cutaneous Melanoma, run by A.J.M. van den Eertwegh.
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 8 inclusion and 4 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 18 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
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 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.
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?
Number of participants with adverse events as assessed by CTCAE V3.0 (time frame: From the time of injection until 28 days after injection of tremelimumab). The study lists 3 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 NCT04274816, 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 18 Feb 2020.