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

Sponsor

A.J.M. van den Eertwegh (Other)

Overall Status

Completed

CT.gov ID

NCT04274816

Collaborator

(none)

Enrollment

Arm

19.6

Actual Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous Melanoma	Drug: Tremelimumab	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

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).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).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official 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)

Actual Study Start Date :

Jul 10, 2012

Actual Primary Completion Date :

Feb 27, 2014

Actual Study Completion Date :

Feb 27, 2014

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

A.J.M. van den Eertwegh

Investigators

Principal Investigator: Tanja D de Gruijl, Amsterdam UMC, location VUmc
Principal Investigator: Alfons JM van den Eertwegh, Amsterdam UMC, location VUmc