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BRF113929: An Open-Label, Two-Cohort, Multicentre Study of GSK2118436 as a Single Agent in Treatment Naïve and Previously Treated Subjects With BRAF Mutation-Positive Metastatic Melanoma to the Brain


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Melanoma and Brain Metastases

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Trial Information

BRF113929: An Open-Label, Two-Cohort, Multicentre Study of GSK2118436 as a Single Agent in Treatment Naïve and Previously Treated Subjects With BRAF Mutation-Positive Metastatic Melanoma to the Brain


Inclusion Criteria:



- Cohort A:

- No prior local therapy for brain metastases.

- Subjects who are receiving concomitant corticosteroids must be on a stable or
decreasing dose for at least 3 weeks prior to first dose of study treatment.

- No prophylactic or preventive anti-epileptic therapy. Exception: anti-epileptic
therapy indicated in order to prevent neurologic symptoms caused by a pre-existing
condition and not related to brain metastasis is allowed.

- Cohort B:

- Subjects must have received at least one local therapy for brain metastases including
but not restricted to brain surgery, Whole Brain Radiotherapy or Stereotactic
Radiosurgery (e.g. gamma knife, linear-accelerated-based radiosurgery, charged
particles, and CyberKnife). Multiple local therapies or combinations of local
therapies are allowed. For subjects receiving local therapy to all brain lesions
(including WBRT), progression of pre-existing lesions based on RECIST 1.1 (> 20%
increase in longest diameter on baseline scan) or new measurable lesions are
required. For subjects receiving local therapy for some but not all lesions, disease
progression based on RECIST 1.1 is not required as long as there are remaining brain
lesions that are measurable and not previously treated.

- Subjects who are receiving concomitant corticosteroids must be on a stable or
decreasing dose for at least 2 weeks prior to first dose of study treatment.

- Prophylactic or preventive anti-epileptic therapy is allowed.

- General:

- Must sign written informed consent.

- Must be at least 18 years of age.

- Histologically confirmed metastatic melanoma (Stage IV), carrying BRAF V600E- or
V600K-mutation.

- Up to two previous treatment regimens for extracranial metastatic melanoma including
chemo-, cytokine-, immuno-, biological- and vaccine-therapy.

- At least one measurable intracranial target lesion for which all of the following
criteria have to be met:

- previously untreated or progressive according to RECIST 1.1 (greater than or equal to
20% increase in longest diameter on baseline scan) after previous local therapy

- immediate local therapy clinically not indicated or patient is not a suitable
candidate to receive immediate local therapy

- largest diameter of greater than or equal to 0.5cm but less than or equal to 4 cm as
determined by contrast-enhanced MRI

- for target lesions (for definition see Section 6.1.1) with diameter of greater than
0.5 cm but less than or equal to 1 cm documented measurement by a neuroradiologist is
required.

- for all lesions with diameter of greater than or equal to 3 cm but less than or equal
to 4 cm documented measurement by a neuroradiologist is required.

- Time interval between last day of previous anti-tumour systemic treatment and first
dose of GSK2118436:

- 14 days elapsed from last treatment with surgery, SRS or gamma knife

- 28 days elapsed from last treatment with WBRT

- Greater than or equal to 28 days or five half-lives (whichever is longer) have
elapsed from last dose of approved or investigational chemo-, cytokine-, immune-,
biological-, or vaccine-therapy.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.

- Adequate organ function.

- Women with child-bearing potential and men with reproductive potential must be
willing to practice acceptable methods of birth control during the study.

- Women of childbearing potential must have a negative serum pregnancy test within 14
days prior to the first dose of study treatment.

Exclusion Criteria:

- Neurological symptoms related to brain metastasis.

- Previous treatment with a BRAF or MEK inhibitor.

- Current or expected use of a prohibited medication during treatment with GSK2118436.

- Presence of leptomeningeal disease or primary dural metastases.

- Known allergies against contrast agents required for magnetic resonance imaging (MRI)
of intracranial lesions.

- Current use of therapeutic warfarin. NOTE: Low molecular weight heparin and
prophylactic low-dose warfarin are permitted.

- Unresolved toxicity of National Cancer Institute Common Terminology Criteria for
Adverse Events, version 4.0 (NCI v4.0) Grade 2 or higher from previous anti-cancer
therapy, except alopecia.

- Presence of active gastrointestinal disease or other condition that will interfere
significantly with the absorption of drugs.

- A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or
Hepatitis C Virus (HCV) infection.

- Acute infection requiring intravenous antibiotics

- History of another malignancy. Exception: (a) Subjects who have been disease-free
for 5 years, (b) a history of completely resected non-melanoma skin cancer, (c)
successfully treated in situ carcinoma, (d) CLL in stable remission, or (e) indolent
prostate cancer requiring no or only anti-hormonal therapy with histologically
confirmed tumour lesions that can be clearly differentiated from melanoma target and
non-target lesions are eligible.

- Certain cardiac abnormalities.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall intracranial response rate (OIRR) in BRAF V600E mutation positive subjects for each cohort

Outcome Time Frame:

Approximately 1.5 years

Safety Issue:

No

Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:

GlaxoSmithKline

Authority:

Italy: Agenzia Italiana del Farmaco

Study ID:

113929

NCT ID:

NCT01266967

Start Date:

February 2011

Completion Date:

November 2012

Related Keywords:

  • Melanoma and Brain Metastases
  • GSK2118436
  • Metastatic melanoma to the brain
  • Brain metastases
  • Braf mutation
  • Brain neoplasm
  • BRAF inhibitor
  • Melanoma
  • Neoplasm Metastasis
  • Brain Neoplasms

Name

Location

GSK Investigational SiteBakersfield, California  93309
GSK Investigational SiteFort Worth, Texas  76104
GSK Investigational SiteRoyal Oak, Michigan  48073
GSK Investigational SitePittsburgh, Pennsylvania  15213
GSK Investigational SiteGermantown, Tennessee  38138
GSK Investigational SiteNew York, New York  10021
GSK Investigational SiteSeattle, Washington  98133