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

NCT ID: NCT01983124

Last Updated: 2016-01-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2015-09-30

Brief 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.

Detailed 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.

Conditions

Malignant Melanoma Stage IV

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fotemustine + Vemurafenib

Fotemustine 100 mg/m2 q21 + Vemurafenib gelatin capsules supplied as 240-mg strengths. Vemurafenib will be administered continuous oral dosing at 960 mg twice daily or dose administered at time of disease progression with Vemurafenib previous treatment.

Group Type: EXPERIMENTAL

Fotemustine + Vemurafenib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Fotemustine; Zelboraf

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Istituto Nazionale per lo Studio e la Cura dei Tumori

OTHER

Sponsor Role: collaborator

Paola Queirolo

OTHER

Sponsor Role: lead

Responsible Party

Paola Queirolo

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Paola Queirolo, MD

Role: PRINCIPAL_INVESTIGATOR

IRCCS AOU San Martino IST

Locations

Paola Queirolo

Genova, , Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori "G.Pascale"

Napoli, , Italy

Countries

Italy

References

Queirolo P, Spagnolo F, Picasso V, Spano L, Tanda E, Fontana V, Giorello L, Merlo DF, Simeone E, Grimaldi AM, Curvietto M, Del Vecchio M, Bruzzi P, Ascierto PA. Combined vemurafenib and fotemustine in patients with BRAF V600 melanoma progressing on vemurafenib. Oncotarget. 2016 Jul 13;9(15):12408-12417. doi: 10.18632/oncotarget.10589. eCollection 2018 Feb 23.

Reference Type: DERIVED

PMID: 29552321 (View on PubMed)

Other Identifiers

2012-004172-18

Identifier Type: -

Identifier Source: org_study_id