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

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.

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Key information

Conditions

Cutaneous Melanoma Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tremelimumab

Drug

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).

Other names: Anti-CTLA-4

Primary outcomes

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)

Sponsors and collaborators

Lead sponsor

A.J.M. van den Eertwegh

Other

Registry information

Official study 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)

Important dates

Study start: 2012
Primary completion: 2014
Study completion: 2014
First posted: Feb 18, 2020
Registry last updated: Feb 18, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed