Intervention: Sapanisertib
Trial phase: Phase 1 | Phase 2
SMILES: CC(C)n1nc(-c2ccc3oc(N)nc3c2)c2c(N)ncnc21
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 5
Group description: Phase 1 dose level 2 participants receive MLN01283 4 mg orally once daily of a 28 day cycle.

Participants are treated indefinitely until disease progression, unacceptable toxicity or withdrawal for other reasons.
Eligibility criteria:
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