Intradermal Injection of Anti-CTLA-4 in Patients With Stage I/II Melanoma

A.J.M. van den Eertwegh

Status and phase: Completed; Phase 1

Conditions: Cutaneous Melanoma

Treatments: Drug: Tremelimumab

Study type: Interventional

Funder types: Other

Identifiers

NCT04274816

2011-000139-10

Details and patient eligibility

About

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.

Full 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.

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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13 participants in 1 patient group

Tremelimumab

Experimental group

Description:

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).

Treatment:

Drug: Tremelimumab