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

Primary Purpose

Malignant Melanoma Stage IV

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Fotemustine + Vemurafenib
Sponsored by
Paola Queirolo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Melanoma Stage IV focused on measuring Advanced Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fotemustine + Vemurafenib

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

First Posted
November 6, 2013
Last Updated
January 19, 2016
Sponsor
Paola Queirolo
Collaborators
Istituto Nazionale per lo Studio e la Cura dei Tumori
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1. Study Identification

Unique Protocol Identification Number
NCT01983124
Brief Title
Vemurafenib + Fotemustine to Treat Advanced Melanoma Patients With V600BRAF Mutation Recurred While on Vemurafenib
Acronym
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
February 2013 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
September 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Paola Queirolo
Collaborators
Istituto Nazionale per lo Studio e la Cura dei Tumori

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Melanoma Stage IV
Keywords
Advanced Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fotemustine + Vemurafenib
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fotemustine + Vemurafenib
Other Intervention Name(s)
Fotemustine, Zelboraf
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression-free survival
Description
To assess activity of vemurafenib in combination with fotemustine, in patients harboring the V600BRAF mutation and recurred while on treatment with Vemurafenib.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Incidence of Grade 3-4 toxicities (any type)
Time Frame
6 months
Title
Rate, duration of response and proportion of patients with duration of response lasting > 24 weeks
Time Frame
6 months
Title
Disease control rate;
Time Frame
6 months
Title
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
Title
Overall survival (OS).
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paola Queirolo, MD
Organizational Affiliation
IRCCS AOU San Martino IST
Official's Role
Principal Investigator
Facility Information:
Facility Name
Paola Queirolo
City
Genova
ZIP/Postal Code
16132
Country
Italy
Facility Name
Istituto Nazionale per lo Studio e la Cura dei Tumori "G.Pascale"
City
Napoli
ZIP/Postal Code
80131
Country
Italy

12. IPD Sharing Statement

Citations:
PubMed Identifier
29552321
Citation
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.
Results Reference
derived

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

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