Clinical trial NCT01586195: Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Malignant Melanoma
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2012-04-26
Enrollment: 31
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Best Objective Response Rate (BORR)
timeFrame: Up to 42 months
Secondary outcomes:
measure: Time to BORR
timeFrame: From start of treatment up to first documentation of confirmed CR or PR (up to 42 months)
measure: Duration of Response
timeFrame: From date of earliest qualifying response up to date of disease progression or death (up to 42 months)
measure: Progression-free Survival (PFS)
timeFrame: From start of treatment up to first documentation of disease progression or death (up to 42 months)
measure: Overall Survival (OS)
timeFrame: Date of first treatment to date of death due to any cause (up to 42 months)
measure: Percentage of Participants With 6-Month Survival
timeFrame: Baseline to Month 6
measure: Percentage of Participants With 12-Month Survival
timeFrame: Baseline to Month 12
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Up to 42 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center
state: Arizona
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA School of Medicine; Hematology/Oncology
state: California
city: Santa Monica
country: United States
facility: The Angeles Clinic and Research Institute, Santa Monica Office
state: California
city: Aurora
country: United States
facility: University of Colorado; Anschutz Cancer Pavilion
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University; Winship Cancer Institute
state: Georgia
city: Park Ridge
country: United States
facility: Oncology Specialists, S.C.
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health System
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Columbus
country: United States
facility: Mid Ohio Onc Hematology Inc
state: Ohio
city: Pittsburgh
country: United States
facility: UPCI Cancer Institute; Cancer Pavillion
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Univ Medical Ctr
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology-Baylor Sammons Cancer Center
state: Texas
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: