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

February 17, 2020 updated by: A.J.M. van den Eertwegh

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: 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).
Drug: Tremelimumab
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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,
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)
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,
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)
7 days after the intradermal injection of tremelimumab

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

A.J.M. van den Eertwegh

Investigators

  • Principal Investigator: Tanja D de Gruijl, Amsterdam UMC, location VUmc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

July 10, 2012

Primary Completion (ACTUAL)

February 27, 2014

Study Completion (ACTUAL)

February 27, 2014

Study Registration Dates

First Submitted

February 6, 2020

First Submitted That Met QC Criteria

February 17, 2020

First Posted (ACTUAL)

February 18, 2020

Study Record Updates

Last Update Posted (ACTUAL)

February 18, 2020

Last Update Submitted That Met QC Criteria

February 17, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-000139-10

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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