Pyrexia Management Using an IL-6 Antibody in BRAF+ Melanoma Patients Treated With Dabrafenib/ Trametinib +/- Immunotherapy

Study Overview
=================
Brief Summary
-----------------
The study examines the development of fever after administration of Actemra (tocilizumab) in patients who have fever and other cytokine release symptoms (headache, nausea, palpitations, low blood pressure) due to cancer therapy (Tafinlar (dabrafenib) / Mekinist (trametinib) +/- immunotherapy) . The goal of the study is to better understand the side effects and to find an effective therapy against them.

Official Title
-----------------
A Phase II, Open Label, Single Arm, Single Center Study to Evaluate Pyrexia Management (With or Without Any Other Cytokine Release Symptoms) Using Tocilizumab, an Humanized Monoclonal Antibody Against the Interleukin - 6 Receptor in BRAF+ Melanoma Patients Treated With Dabrafenib/ Trametinib +/- Immunotherapy

Conditions
-----------------
Pyrexia

Intervention / Treatment
-----------------
* Drug: Actemra


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed Consent as documented by signature Subjects (males and females) age ≥ 18 years ECOG < 3 Subjects with pyrexia grade 1*- 4 and elevated CRP with persistent fever after one day of antipyretic therapy with or without at least one other additional symptom of cytokine release syndrome such as nausea, headache, tachycardia, hypotension, maculopapular rash, shortness of breath, transaminitis, renal failure, dehydration Elevated CRP serum levels further than normal baseline levels (> 3.0 mg/L) Subjects with resected, non-resectable, adjuvant or metastatic BRAF+ melanoma treated with : BRAF inhibitor (dabrafenib) in combination with MEK inhibitor (trametinib) BRAF inhibitor (dabrafenib) in combination with MEK inhibitor (trametinib) preceded by therapy with anti-PD-1/PD-L1 and/or anti CTLA-4 inhibitor BRAF inhibitor (dabrafenib) in combination with MEK inhibitor (trametinib) plus anti-PD- 1/PD-L1 inhibitor

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment arm<br>The patients will be administered Tocilizmab (Actemra) at the following dosage : First dose: 8mg/kg, max. 800mg iv. during 60min If necessary second dose: 8mg/kg, max. 800mg iv. during 60min after 20-36 hours from first dose | Drug: Actemra<br>* Dosage: 8mg/kg (max. 800mg) Actemra administered intravenously as an infusion over 60 min.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pyrexia management | The primary outcome represents the proportion of patients that reduce to at least <38°C after tocilizumab infusion in BRAF+ melanoma patients under treatment with dabrafenib/trametinib +/- immunotherapy - pyrexia status will be assessed at screening visit and on every other defined visit until remission, by assessing body temperature. | 1 hour to up to 72 hours. |