We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Vemurafenib + Fotemustine to Treat Advanced Melanoma Patients With V600BRAF Mutation Recurred While on Vemurafenib (BeyPro1)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01983124
First Posted: November 13, 2013
Last Update Posted: January 20, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Istituto Nazionale per lo Studio e la Cura dei Tumori
Information provided by (Responsible Party):
Paola Queirolo, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
  Purpose
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.

Condition Intervention Phase
Malignant Melanoma Stage IV Drug: Fotemustine + Vemurafenib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Paola Queirolo, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months ]
    To assess activity of vemurafenib in combination with fotemustine, in patients harboring the V600BRAF mutation and recurred while on treatment with Vemurafenib.


Secondary Outcome Measures:
  • Incidence of Grade 3-4 toxicities (any type) [ Time Frame: 6 months ]
  • Rate, duration of response and proportion of patients with duration of response lasting > 24 weeks [ Time Frame: 6 months ]
  • Disease control rate; [ Time Frame: 6 months ]
  • Time to progression of brain metastases (BM), Including incidence of BM in pts free from BM at the time of enrolment [ Time Frame: 6 months ]
  • Overall survival (OS). [ Time Frame: 6 months ]

Enrollment: 31
Study Start Date: February 2013
Study Completion Date: September 2015
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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.

Other Names:
  • Fotemustine
  • Zelboraf

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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01983124


Locations
Italy
Paola Queirolo
Genova, Italy, 16132
Istituto Nazionale per lo Studio e la Cura dei Tumori "G.Pascale"
Napoli, Italy, 80131
Sponsors and Collaborators
Paola Queirolo
Istituto Nazionale per lo Studio e la Cura dei Tumori
Investigators
Principal Investigator: Paola Queirolo, MD IRCCS AOU San Martino IST
  More Information

Responsible Party: Paola Queirolo, MD, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
ClinicalTrials.gov Identifier: NCT01983124     History of Changes
Other Study ID Numbers: 2012-004172-18
First Submitted: November 6, 2013
First Posted: November 13, 2013
Last Update Posted: January 20, 2016
Last Verified: January 2016

Keywords provided by Paola Queirolo, IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy:
Advanced Melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Vemurafenib
Fotemustine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action