Pyrexia Management Using an IL-6 Antibody in BRAF+ Melanoma Patients Treated with Dabrafenib/ Trametinib +/- Immunotherapy (Nov IIT- Pyrex)

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

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.

Study Overview

• Status: Terminated
• Conditions: Pyrexia
• Intervention / Treatment: Drug: Actemra

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8058
    • University Hospital Zurich, Clinic of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Informed Consent as documented by signature
2. Subjects (males and females) age ≥ 18 years
3. ECOG < 3
4. 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
5. Elevated CRP serum levels further than normal baseline levels (> 3.0 mg/L)

6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Treatment arm; 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; Dosage: 8mg/kg (max. 800mg) Actemra administered intravenously as an infusion over 60 min.

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.

Collaborators and Investigators

• Sponsor: University of Zurich

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Actual): October 31, 2021
• Study Completion (Actual): October 31, 2021

Study Registration Dates

• First Submitted: November 26, 2020
• First Submitted That Met QC Criteria: November 26, 2020
• First Posted (Actual): December 3, 2020

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever
• Other Study ID Numbers: NovartisIIT/ 2020-01929

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No