A Randomized Controlled Phase II Trial With Intradermal IMO-2125 in Pathological Tumor Stage (p) T3-4 cN0M0 Melanoma

Study Overview
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Brief Summary
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Currently, there is no widely used adjuvant treatment available to improve survival after surgical excision of a primary melanoma. In a previous study, loco-regional and systemic immune stimulations, as well as favourable clinical outcomes in terms of sentinel lymph node (SLN) tumor status and recurrence-free survival (RFS) in patients with clinical stage I-II melanoma who received a low dose of toll-like receptor 9 (TLR-9) CPG7909 (CpG-B ODN) intradermally at the excision site of the primary tumor prior to SLN biopsy (SNB) were described. In this phase II trial the investigators had investigated the clinical activity of a next-generation CpG-ODN, IMO-2125, and it's ability to induce loco-regional and systemic immune stimulation in pT3-4 cN0M0 melanoma patients who are scheduled to undergo a combined re-excision and SNB is

Official Title
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A Randomized Controlled Phase II Clinical Trial With Intradermal IMO-2125 (Tilsotolimod) in pT3-4 cN0M0 Melanoma

Conditions
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Malignant Melanoma

Intervention / Treatment
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* Drug: Tilsotolimod
* Drug: Saline (0.9% sodium chloride)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Histologically confirmed primary malignant melanoma cutis with a Breslow tumor depth >2.0 mm Scheduled to undergo a combines re-excision and sentinel node biopsy (SNB) World Health Organization (WHO) Performance Status ≤1 Agreement to use effective contraceptive methods from screening until at least 90 days after the IMO-2125 administration Written informed consent Exclusion Criteria: Known hypersensitivity to any oligodeoxynucleotide Active auto-immune disease requiring disease-modifying therapy at the tumr of screening Pathologically confirmed loco-regional or distant metastasis Non-skin melanoma Patients with another primary malignancy (some exceptions) Active systemic infections requiring antibiotics Women who are pregnant or breast-feeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Randomized Controlled Phase II Multicenter Clinical Trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tilsotolimod (IMO-2125)<br>Intradermal, single injection of 1 ml (8 mg) Tilsotolimod (IMO-2125) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB). | Drug: Tilsotolimod<br>* Intradermal, single injection of 1 ml (8 mg) Tilsotolimod (IMO-2125) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).<br>* Other names: IMO-2125;|
| Placebo Comparator: Placebo<br>Intradermal, single injection of 1 ml plain saline (0.9% sodium chloride) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB). | Drug: Saline (0.9% sodium chloride)<br>* Intradermal, single injection of 1 ml plain saline (0.9% sodium chloride) at the primary melanoma excision site, one week prior to sentinel node biopsy (SNB).<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of tumor positive sentinal lymph node (SLN) | The rate of tumor positive sentinal lymph node (SLN) | Seven days after the intradermal injection of Tilsotolimod (IMO-2125) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response in the SLN and peripheral blood | Frequency and activation state of lymph node resident (LNR) conventional dendritic cells (DC) and melanoma antigen-specific T cell responses in the SLN and peripheral blood. | Seven days after the intradermal injection of Tilsotolimod (IMO-2125) | 
| Recurrence free survival (RFS) | The length of time from intradermal injection of Tilsotolimod (IMO-2125) to first documentation of recurrence. | At 5 years and 10 years after sentinel node biopsy (SNB) | 
| Overall survival | The length of time from intradermal injection of Tilsotolimod (IMO-2125) to death from any cause. | At 5 years and 10 years after sentinel node biopsy (SNB) |