Phase 2 Study of Neoadjuvant Vemurafenib in Melanoma Patients With Untreated Brain Metastases

NCT01781026 | Completed Phase 2 Results DMC

• 1 other identifier: 1208010666
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to study the activity of vemurafenib in untreated melanoma brain metastases harboring B-Raf proto-oncogene, serine/threonine kinase (BRAF) mutations that are not amenable to stereotactic radiosurgery based on size, number of lesions or location, to measure cerebrospinal fluid (CSF) levels of vemurafenib as an indicator of central nervous system penetrance and to measure levels of vemurafenib in normal brain tissue and brain metastases in those in whom surgical management is feasible.

Conditions

Melanoma

Keywords

B-raf V600E; V600K mutation; metastatic melanoma

Outcome Measures

Primary Outcomes (1)

• Activity of Vemurafenib in Untreated Brain Metastases

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  1 year

Study Arms (1)

Vemurafenib Administration

EXPERIMENTAL

Vemurafenib 960 mg orally, twice per day

Drug: Vemurafenib

Interventions

Vemurafenib DRUG

Single arm trial

Also known as: Zelboraf / RO5185426

Vemurafenib Administration

Eligibility Criteria

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

You may qualify if:

• Biopsy proven metastatic melanoma with the B-raf V600E or V600K mutations.
• Untreated brain metastases
• At least one cerebral metastasis that is not amenable to stereotactic radiosurgery (SRS) or surgical resection based on size or location OR four or more lesions
• Patients may be symptomatic at the time of enrollment, but after any necessary local therapy and/or corticosteroids, the patient should be asymptomatic when vemurafenib is initiated.
• Age \>18
• Adequate organ function
• ECOG performance status \< 3
• No prior therapies with selective inhibitors of mutated BRAF; other prior therapies must have been administered at least 4 weeks before administration of vemurafenib
• Life expectancy of at least 3 months
• Understanding and willingness to consent
• The use of corticosteroids to control cerebral edema or treat symptoms will be allowed
• A history of whole brain radiotherapy for brain metastases is allowed, but any stable lesion that was present at the time of WBRT will NOT be considered evaluable. A minimum of 1 week break will be required between prior WBRT and initiation of vemurafenib therapy.

You may not qualify if:

• Presence of leptomeningeal disease based on positive CSF cytology.
• History or presence of clinically significant ventricular or atrial dysrhythmias ≥ Grade 2 (NCI CTCAE, v4.0), Corrected QT (QTc) interval \>450 ms at baseline or history of congenital long QT syndrome
• Uncontrolled medical illness, such as uncontrolled infection, congestive heart failure and MI within 2 months.
• Second active, untreated malignancy, which is likely to result in the patient's demise prior to death from uncontrolled melanoma CNS metastases. This will be determined on a case by case basis by the PIs.
• Unwillingness to undergo monitoring for a secondary malignancy including clinical dermatologic examinations and head and neck examinations and serial CT scans.

Sponsors & Collaborators

• Yale University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

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

Results Point of Contact

• Title: Harriet Kluger
• Organization: Yale University

Harriet.Kluger@yale.edu

Study Officials

• Harriet M Kluger, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: January 29, 2013
• First Posted: January 31, 2013
• Study Start: April 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: June 1, 2014
• Last Updated: March 10, 2017
• Results First Posted: April 2, 2015

Record last verified: 2017-01

Locations

US (1)