Vemurafenib + Fotemustine to Treat Advanced Melanoma Patients With V600BRAF Mutation Recurred While on Vemurafenib

Malignant Melanoma Stage IV Clinical Trial

— BeyPro1  

Official title:

A Phase II Single-arm Study for the Treatment After Recurrence of Advanced Melanoma Patients Harboring the V600BRAF Mutation and Pretreated With Vemurafenib, With the Association of Vemurafenib Plus Fotemustine.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01983124
• Other study ID #: 2012-004172-18
• Status: Completed
• Phase: Phase 2
• First received: November 6, 2013
• Last updated: January 19, 2016
• Start date: February 2013
• Est. completion date: September 2015

Study information

• Verified date: January 2016
• Source: IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the activity of Vemurafenib in combination with Fotemustine in Patients with unresectable Stage IV melanoma harboring V600 BRAF mutation who recurred while in treatment with Vemurafenib. In addition the feasibility and safety profile of prolonging treatment of this drugs combination will be assessed.

Description:

Patients are treated with Fotemustine 100 mg/m2 q21 + Vemurafenib. Vemurafenib will be administered continuous oral dosing at 960 mg twice daily or dose administered at time of disease progression with Vemurafenib previous treatment (720 or 480 mg).Treatment will be continued until progression or unacceptable toxicity. The Progression-free survival will be assessed as primary endpoint, other outcomes(i.e., incidence of grade III-IV toxicity, Disease Control Rate, and Overall Survival) will be considered secondary endpoints.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 2015
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed melanoma harboring the V600 mutation

• Unresectable Stage IV melanoma

• At least 18 y of age

• Eastern Cooperative Oncology Group (ECOG) performance status of <2

• In progression during treatment with Vemurafenib

• At least 2 weeks since the last radiotherapy treatment

• Life expectancy >12 weeks

• Clinical laboratory values at screening defined as follow: lactate dehydrogenase (LDH) < 2.0 x upper limit of normal (ULN), Hemoglobin >9 g/dL, Absolute neutrophil count 1500/mm3, Platelet count >100,000/mm3, Creatinine <1.5 mg/dL (NOTE: If creatinine is >1.5 mg/dL, subject is eligible if creatinine clearance > 60 mL/min using the Cockgroft-Gault equation), Total bilirubin <1.5 x ULN, Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) <2.5 x ULN

• Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for = 1 year

• Fertile men and women must use an effective method of contraception

• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Female subjects who are pregnant or nursing

• Female subjects of childbearing potential or males not using or not willing to use two forms of effective contraception

• Any of the following within the 6 months prior to randomization: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, hypertension not adequately controlled by current medications

• Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc) other than those administered in this study

• Known hypersensitivity to Vemurafenib or another BRAF inhibitor

• History of congenital long QT syndrome, history or presence of clinically significant ventricular or atrial dysrhythmias = Grade 2 (NCI Common Toxicity Criteria for Adverse Effects (CTCAE) Version 4.0

• Corrected QT (QTc) interval = 500 msec at baseline

• Uncontrolled medical illness (such as infection requiring treatment with intravenous (IV) antibiotics)

• Has had surgery within 2 weeks (1 week for minor surgery, eg, procedures requiring only local anesthetics) prior to the first dose of study medication

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malignant Melanoma Stage IV
• Melanoma

Intervention

Drug:
• Fotemustine + Vemurafenib
Fotemustine 100mg/m2 IV on day 1 of each 21 day cycle. Number of cycles: until progression or unacceptable toxicity. Vemurafenib administered continuous oral dosing 960 mg twice daily or dose administered at time of progression since progression or unacceptable toxicity.

Locations

Country	Name	City	State
Italy	Paola Queirolo	Genova
Italy	Istituto Nazionale per lo Studio e la Cura dei Tumori "G.Pascale"	Napoli

Sponsors (2)

Lead Sponsor	Collaborator
Paola Queirolo	Istituto Nazionale per lo Studio e la Cura dei Tumori

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival	To assess activity of vemurafenib in combination with fotemustine, in patients harboring the V600BRAF mutation and recurred while on treatment with Vemurafenib.	6 months	No
Secondary	Incidence of Grade 3-4 toxicities (any type)		6 months	Yes
Secondary	Rate, duration of response and proportion of patients with duration of response lasting > 24 weeks		6 months	No
Secondary	Disease control rate;		6 months	No
Secondary	Time to progression of brain metastases (BM), Including incidence of BM in pts free from BM at the time of enrolment		6 months	No
Secondary	Overall survival (OS).		6 months	No