Vemurafenib Plus Cobimetinib After Radiosurgery in Patients With BRAF-mutant Melanoma Brain Metastases

Phase 2

Terminated

• Conditions: Malignant Melanoma Stage IV; BRAF V600 Mutation; Brain Metastases
• Interventions: Drug: Vemurafenib; Drug: Cobimetinib

• Registration Number: NCT03430947
• Lead Sponsor: Technische Universität Dresden

Brief Summary

This is a phase II, open label, non-randomised study of vemurafenib and cobimetinib after radiosurgery in adult patients with BRAFV600-mutant melanoma brain metastases. All patients will receive vemurafenib 960 mg twice a day on days 1 - 28 combined with cobimetinib 60 mg once a day on days 1 - 21 of each 28-day treatment cycle until disease progression, drug toxicity or death.

The primary objective of this study is to determine the best overall response rate (BORR) in the brain. The extracranial BORR, intra- and extracranial duration of response, progression-free survival and overall survival, adverse events, quality of life and radiomics features predicting long-term local control of brain metastases and treatment-related toxicity will also be examined.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-01-10
• Study First Submitted QC: 2018-02-06
• Study First Posted: 2018-02-13
• Study Start: 2018-07-01
• Primary Completion: 2023-02-10
• Study Completion: 2023-02-10
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-12
• Last Update Posted: 2023-09-14

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	Vemurafenib	all patients will be treated with Vemurafenib + Cobimetinib
Treatment	Cobimetinib	all patients will be treated with Vemurafenib + Cobimetinib

Primary Outcome Measures

Name	Time	Method
Best overall response rate in the brain	2 years	rate of patients with complete response or partial response (intracranial)

Secondary Outcome Measures

Name	Time	Method
Extracranial best overall response rate	2 years	rate of patients with complete response or partial response (extracranial)
Best overall response rate calculated for the whole body tumor sites	2 years	rate of patients with complete response or partial response
Intracranial duration of response	2 years	time from best overall response in the brain to first documentation of intracranial progression
Extracranial duration of response	2 years	time from best extracranial overall response to first documentation of extracranial progression
Radiomics for intracranial Treatment-related toxicity	every 6 weeks up to 2 years	Radiomics features predicting treatment-related toxicity (e.g. radionecrosis, hemorrhage, edema) using Magnetic Resonance Imaging
Progression-free survival	2 years	time from first dose of study treatment until progression
Overall survival	2 years	time from first dose of study treatment until death due to any cause
Incidence of adverse events	2 years	Adverse events by type, frequency and severity using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.03; number of patients who withdraw from the study due to intolerable adverse events.
Radiomics for long-term control of brain metastases	every 6 weeks up to 2 years	Radiomics features predictive of long-term local control of brain metastases using Magnetic Resonance Imaging

Trial Locations

Locations (3)

Technische Universität Dresden; 🇩🇪 Dresden, Germany

Ruprecht-Karls-University of Heidelberg, Faculty of Medicine; 🇩🇪 Heidelberg, Germany

Eberhard Karls University of Tübingen, University Medical Center; 🇩🇪 Tuebingen, Germany