MLN0128 in Recurrent/Metastatic Merkel Cell Carcinoma

Inclusion Criteria

• Metastatic or recurrent MCC confirmed by histology
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral CT scan (see section 10 for the evaluation of measureable disease). Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented
• Age 18 years or older
• ECOG performance status ≤ 2
• Participants must have normal organ and marrow function
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit

--- OR

• Are surgically sterile --- OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time
• Male patients, even if surgically sterilized (ie, status post-vasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
• Agree to completely abstain from heterosexual intercourse
• Treatment with strong CYP2C19, CYP3A4, and CYP2C9 inhibitors and/or inducers
• Tissue for correlative studies must be available (paraffinized or frozen)
• Ability to swallow oral medications and maintain an empty stomach state for 2 hours prior to the MLN0128 dose and for 1 hour following administration
• Ability to understand and the willingness to sign a written informed consent

Exclusion Criteria

• Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study
• The subject has active brain metastases or epidural disease
• Participants who are receiving any other investigational agents within 14 days before the first dose of study drug
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of MLN0128
• Poorly controlled diabetes mellitus
• History of any of the following within the last 6 months prior to study entry:
• Ischemic myocardial event
• Ischemic cerebrovascular event
• Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia
• Placement of a pacemaker for control of rhythm
• New York Heart Association (NYHA) Class III or IV heart failure
• Pulmonary embolism
• Significant active cardiovascular or pulmonary disease at the time of study entry, including:
• Uncontrolled high blood pressure
• Pulmonary hypertension
• Uncontrolled asthma
• Significant valvular disease; severe regurgitation or stenosis
• Medically significant (symptomatic) bradycardia
• History of arrhythmia requiring an implantable cardiac defibrillator
• Baseline prolongation of the rate-corrected QT interval (QTc)
• Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids