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

NCT01983124 | Completed Phase 2

• 1 other identifier: 2012-004172-18
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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.

Conditions

Malignant Melanoma Stage IV

Keywords

Advanced Melanoma

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Incidence of Grade 3-4 toxicities (any type)

  6 months

• Rate, duration of response and proportion of patients with duration of response lasting > 24 weeks

  6 months

• Disease control rate;

  6 months

• Time to progression of brain metastases (BM), Including incidence of BM in pts free from BM at the time of enrolment

  6 months

• Overall survival (OS).

  6 months

Study Arms (1)

Fotemustine + Vemurafenib

EXPERIMENTAL

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.

Drug: Fotemustine + Vemurafenib

Interventions

Fotemustine + Vemurafenib 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.

Also known as: Fotemustine, Zelboraf

Fotemustine + Vemurafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Paola Queirolo: lead
• Istituto Nazionale per lo Studio e la Cura dei Tumori: collaborator

Study Sites (2)

Paola Queirolo

Genova, 16132, Italy

Location

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

Napoli, 80131, Italy

Location

Related Publications (1)

• 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.

  PMID: 29552321 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

fotemustine; Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Paola Queirolo, MD

  IRCCS AOU San Martino IST

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: November 6, 2013
• First Posted: November 13, 2013
• Study Start: February 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: September 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

IT (2)