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

NCT04274816 | Completed Phase 1

• 1 other identifier: 2011-000139-10
• Study Type: interventional
• Target: 13
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Cutaneous Melanoma

Keywords

Stage I-II melanoma; Anti-CTLA-4; Immunotherapy; Neoadjuvant

Outcome Measures

Primary Outcomes (3)

• 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

  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)

  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)

  7 days after the intradermal injection of tremelimumab

Study Arms (1)

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).

Drug: Tremelimumab

Interventions

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).

Also known as: Anti-CTLA-4

Tremelimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• A.J.M. van den Eertwegh: lead

Related Publications (1)

• 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.

  PMID: 35857579 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

tremelimumab; Ipilimumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tanja D de Gruijl

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

• Alfons JM van den Eertwegh

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 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).

Study Record Dates

• First Submitted: February 6, 2020
• First Posted: February 18, 2020
• Study Start: July 10, 2012
• Primary Completion: February 27, 2014
• Study Completion: February 27, 2014
• Last Updated: February 18, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share