Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E

An Open-Label, Multicenter, Phase II Study Of Continuous Oral Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E

This is an open-label, multicenter, single-agent, phase II study of continuous oral Zelboraf (vemurafenib) in participants with locally-advanced, unresectable, stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.

Study Overview

• Status: Terminated
• Conditions: Malignant Melanoma
• Intervention / Treatment: Drug: Vemurafenib

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA School of Medicine; Hematology/Oncology
    • Santa Monica, California, United States, 90025
      • The Angeles Clinic and Research Institute, Santa Monica Office
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado; Anschutz Cancer Pavilion
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University; Winship Cancer Institute
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Oncology Specialists, S.C.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Atlantic Health System
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43219
      • Mid Ohio Onc Hematology Inc
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPCI Cancer Institute; Cancer Pavillion
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Univ Medical Ctr
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Sammons Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
• Histologically-confirmed metastatic melanoma (unresectable Stage IIIc or IV) with an activating BRAF mutation other than V600E, as detected by DNA sequencing of exon 15 performed at a centralized laboratory
• Measurable disease (as defined by RECIST, v1.1)
• Adequate recovery from most recent systemic or local treatment for cancer
• Adequate organ function within 28 days prior to initiation of treatment
• For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib
• For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib
• Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women. Women who are either surgically sterile or have been post-menopausal for at least 1 year are eligible to participate in this study
• Agreement not to donate blood or blood products during the study and for at least 6 months after discontinuation of vemurafenib; for male participants, agreement not to donate sperm during the study and for at least 6 months after discontinuation of vemurafenib
• Signed informed consent form (prior to study entry and before performing any study-related procedures)

Exclusion Criteria:

• Invasive malignancy other than melanoma at the time of enrollment and within 2 years prior to first study drug administration, except for adequately treated (with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years
• Pregnant or breast-feeding
• Inability to swallow pills
• Concurrent anti-tumor therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, including participation in an experimental drug study)
• Radiation therapy </= 1 week prior to first administration of vemurafenib and stereotactic radiotherapy </= 1 day prior to first administration of vemurafenib
• Prior treatment with a BRAF or MEK inhibitor
• Either a concurrent condition (including medical illness, such as active infection requiring treatment with IV antibiotics or the presence of laboratory abnormalities) or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
• History of congenital long QT syndrome or a corrected QT (QTc) interval > 450 ms at baseline
• Ongoing cardiac dysrhythmia >/= Grade 2
• Unwillingness to practice effective birth control
• Inability to comply with other requirements of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vemurafenib; Participants with untreated or previously treated locally advanced, unresectable, Stage IIIc or metastatic melanoma who have an activating exon 15 BRAF mutation other than V600E received vemurafenib 960 milligram (mg) orally twice daily (BID) until disease progression.	Drug: Vemurafenib; Vemurafenib 960 mg BID; Other Names: Zelboraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Objective Response Rate (BORR)	BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants whose best overall response was a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper-Pearson.	Up to 42 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to BORR	In participants with a confirmed CR or PR, time to BORR was defined as the interval between the date of first treatment and the date of first documentation of confirmed CR or PR (whichever occurred first). BORR was assessed by the investigators according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. Participants without confirmed CR or PR were censored at the date of last tumor assessment. The time to response was summarized using univariate statistics.	From start of treatment up to first documentation of confirmed CR or PR (up to 42 months)
Duration of Response	In participants with a confirmed CR or PR, duration of response was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Duration of response was summarized using Kaplan-Meier method.	From date of earliest qualifying response up to date of disease progression or death (up to 42 months)
Progression-free Survival (PFS)	PFS was assessed by the investigators according to RECIST v1.1 and defined as the time interval between the date of the first treatment dose and the date of disease progression or death due to any cause, whichever occurred first. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. PFS was summarized using Kaplan-Meier method.	From start of treatment up to first documentation of disease progression or death (up to 42 months)
Overall Survival (OS)	OS was defined as the time from the date of first treatment to the date of death due to any cause. OS was summarized using Kaplan-Meier method.	Date of first treatment to date of death due to any cause (up to 42 months)
Percentage of Participants With 6-Month Survival		Baseline to Month 6
Percentage of Participants With 12-Month Survival		Baseline to Month 12
Number of Participants With an Adverse Event (AE)	An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.	Up to 42 months

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2011
• Primary Completion (Actual): April 30, 2015
• Study Completion (Actual): April 30, 2015

Study Registration Dates

• First Submitted: April 24, 2012
• First Submitted That Met QC Criteria: April 24, 2012
• First Posted (Estimate): April 26, 2012

Study Record Updates

• Last Update Posted (Actual): May 25, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Vemurafenib
• Other Study ID Numbers: ML27763