A Phase I Study of Oral LGX818 in Adult Patients With Advanced or Metastatic BRAF Mutant Melanoma
Phase: Phase 1
Diagnosis: Cutaneous Skin Cancer
NCT ID: NCT01436656
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 11-246
CLGX818X2101 is a first-time in-human, phase I study to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of daily administered LGX818 (daily, twice daily and/or every-other-day), a RAF kinase inhibitor. Patients with locally advanced or metastatic melanoma harboring the BRAF V600 mutation (during dose escalation phase and expansion phase) and patients with metastatic colorectal cancer harboring the BRAF V600 mutation (during the expansion phase) will be enrolled. The study consists of a dose escalation part were cohorts of patients will receive escalating oral doses of LGX818, followed by a safety dose expansion part were patients will be treated with oral dose of LGX818 given at the MTD or RP2D.
Massachusetts General Hospital, Beth-Israel Deaconess Medical Center
Keith Flaherty, MD,
Massachusetts General Hospital
Daniel Cho, MD,
Beth Israel Deaconess Medical Center
Massachusetts General Hospital:
Cancer Trials Call Center, 877-789-6100
Beth-Israel Deaconess Medical Center:
Cancer Trials Call Center, 617-667-3060
For the dose escalation phase:
1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage
IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion
phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic
melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii)
confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC)
for which no further effective standard therapy exists.
2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
3. Evidence of measurable disease, defined as at least one lesion that can accurately be
measured in at least one dimension as ≥ 20 mm with conventional techniques or ≥ 10 mm
with spiral CT scan; cutaneous lesions must have clearly defined margins and measure
≥ 5 mm in at least one diameter.
1. Previous therapy with a MEK inhibitor.
2. Symptomatic or untreated leptomeningeal disease.
3. Symptomatic or untreated brain metastasis.Patients previously treated for these
conditions that are asymptomatic in the absence of corticosteroid therapy are allowed
to enroll. Brain metastasis must be stable with verification by imaging.
4. Known acute or chronic pancreatitis.
5. Clinically significant cardiac disease
6. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral LGX818
7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include:
adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the
cervix, treated curatively and without evidence of recurrence for at least 3 years
prior to study entry; or other solid tumor treated curatively, and without evidence
of recurrence for at least 3 years prior to study entry.
8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 5 mIU/mL).
9. History of thromboembolic or cerebrovascular events within the last 6 months
Other protocol-defined inclusion/exclusion criteria may apply