Cutaneous Melanoma
Conditions
Keywords
Stage I-II melanoma, Anti-CTLA-4, Immunotherapy, Neoadjuvant
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.
Interventions
DRUGTremelimumab
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).
Sponsors
A.J.M. van den Eertwegh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Outcome results
None listed