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

Phase 1

Completed

• Conditions: Cutaneous Melanoma
• Interventions: Drug: Tremelimumab

• Registration Number: NCT04274816
• Lead Sponsor: A.J.M. van den Eertwegh

Brief 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). 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 Timeline

• Study Start: 2012-07-10
• Primary Completion: 2014-02-27
• Study Completion: 2014-02-27
• Status Verified: 2020-02
• Study First Submitted: 2020-02-06
• Study First Submitted QC: 2020-02-17
• Last Update Submitted: 2020-02-17
• Study First Posted: 2020-02-18
• Last Update Posted: 2020-02-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tremelimumab	Tremelimumab	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).

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events as assessed by CTCAE V3.0	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,	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,	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)