Sapanisertib in Treating Patients with Recurrent or Metastatic Merkel Cell Cancer

Inclusion Criteria

• Metastatic or recurrent merkel cell carcinoma (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 computed tomography (CT) scan; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL
• Total bilirubin within normal institutional limits
• Aspartate aminotransaminase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
• Creatinine within normal institutional limits, OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
• Fasting serum glucose =< 130 mg/dL
• Fasting triglycerides =< 300 mg/dL
• 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, from the time of signing the informed consent through 90 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse; periodic abstinence (calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception)
• 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 120 days after the last dose of study drug, or * Agree to completely abstain from heterosexual intercourse; periodic abstinence (calendar, ovulation, symptothermal, postovulation methods for the female partner) and withdrawal are not acceptable methods of contraception * Agree not to donate sperm during the course of this study or 120 days after receiving their last dose of study drug
• Treatment with strong cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19), cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), and cytochrome P450 family 2 subfamily C member 9 (CYP2C9) inhibitors and/or inducers must be discontinued at least 1 week before administration of the first dose of study drug
• Tissue for correlative studies must be available (paraffinized or frozen), but confirmation at screening is not needed; archival tissue may be used instead of a fresh biopsy at baseline if it already exists
• 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 document before performance of any study related procedure not part of standard medical care

Exclusion Criteria

• Participants who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• The subject has active brain metastases or epidural disease (Note: Subjects with brain metastases previously treated with whole brain radiation or radiosurgery or subjects with epidural disease previously treated with radiation or surgery who are asymptomatic and do not require steroid treatment for at least 2 weeks before starting study treatment are eligible)
• 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 that would limit compliance with study requirements
• 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 defined as glycosylated hemoglobin measurement (HbA1c) > 7%; subjects with a history of transient glucose intolerance due to corticosteroid administration are allowed in this study if all other inclusion/exclusion criteria are met
• History of any of the following within the last 6 months prior to study entry: *Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures * Ischemic cerebrovascular event, including transient ischemic attack (TIA) and artery revascularization procedures * Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia) * 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 (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg) * Pulmonary hypertension * Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air * Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement * Medically significant (symptomatic) bradycardia * History of arrhythmia requiring an implantable cardiac defibrillator * Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)
• Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids (either intravenous [IV] or oral steroids, excluding inhalers) within 1 week before administration of the first dose of study drug (patients already receiving erythropoietin on a chronic basis for >= 4 weeks are eligible)
• Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease; patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection