Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma

Inclusion Criteria:

• Willing and able to provide written Institutional Review Board (IRB)/IndependentEthics Committee (IEC)-approved informed consent. For subjects < 18 years of age,their parents or legal guardians must sign a written informed consent. Assent, whenappropriate, will be obtained according to institutional guidelines

• Have histologically or cytological confirmed diagnosis of rhabdomyosarcoma withlocally advanced/unresectable, metastatic, refractory or relapsed disease who havefailed standard therapy and for whom no known curative therapy exists

• Measurable disease according to RECIST version 1.1

• Prior cancer therapy: Subjects may have received any number of prior therapyregimens. In the investigator's opinion, subjects must have tolerated priorcytotoxic therapies well and have adequate bone marrow reserve. At the time oftreatment initiation, at least 3 weeks must have elapsed after prior cytotoxicchemotherapy. At least 7 days must have elapsed since completion of any priornon-cytotoxic cancer therapy and any associated AEs must have resolved

• Prior radiotherapy is allowed if >= 2 weeks have elapsed for local palliativeradiation therapy (XRT) (small port); >= 6 months must have elapsed if prior totalbody irradiation, craniospinal XRT or if > 50% radiation of the pelvis; > 6 weeksmust have elapsed if other substantial bone marrow radiation (defined per principalinvestigator's [PI's] discretion). Subjects who have received brain irradiation musthave completed whole brain radiotherapy and/or gamma knife at least 4 weeks prior toenrollment

• Subjects with controlled asymptomatic central nervous system (CNS) involvement areallowed in absence of therapy with anticonvulsants. Subjects not requiring steroidsor requiring steroids at a stable dose (=< 4 mg/day dexamethasone or equivalent) forat least 2 weeks are eligible

• Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancertherapy to National Cancer Institute (NCI) Common Terminology Criteria for AdverseEvents (CTCAE) (version 4.03) grade < 1 or to the baseline laboratory values asdefined below

• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =< 2 in subjects >= 17 years old; or Karnofsky/Lansky > 50 in subjects < 16 years old

• Subjects age > 18 years for first cohort. Subjects must be > 12 years old for thesecond and subsequent cohorts

• Life expectancy of at least 3 months

• Absolute neutrophil count (ANC) >= 1000/mm^3 (>= 1.0 x 10^9/L)

• Platelets (PLT) >= 100,000/mm^3 (>= 100 x 10^9/L) (transfusion independent, definedas not receiving platelet transfusions within a 7 day period prior to screening)

• Hemoglobin > 9.0 g/dL (transfusions are allowed)

• Serum creatinine =< 1.5 x upper limit of normal (ULN) or creatinine clearance > 60mL/min

• Total serum bilirubin =< 1.5 x ULN; =< 5 x ULN if Gilbert's syndrome

• Liver transaminases (aspartate aminotransferase [AST]/alanine aminotransferase [ALT]) =< 2.5 x ULN; =< 5 x ULN if liver metastases are present

• Pregnancy test if female of child-bearing potential negative within 7 days ofstarting treatment

• Cardiac ejection fraction > 50% or shortening fraction > 28% by echocardiography (ECHO) or multigated acquisition scan (MUGA)

• Females of child-bearing potential must have a negative pregnancy test duringscreening and be neither breastfeeding nor intending to become pregnant during studyparticipation. Females of childbearing potential must agree to avoid pregnancyduring the study and commit to abstinence from heterosexual intercourse or agree touse two methods of birth control (one highly effective method and one additionaleffective method) at least 4 weeks before the start of protocol therapy, for theduration of study participation, and for 6 months after the last dose ofmocetinostat

• Males with partner(s) of childbearing potential must take appropriate precautions toavoid fathering a child from the screening period until 90 days after receiving thelast dose of mocetinostat. They must commit to abstinence from heterosexualintercourse or agree to use appropriate barrier contraception

• Prior to enrollment of females or males of reproductive potential, the investigatormust document confirmation of the subject's understanding of the possibleteratogenic effects of mocetinostat

• Willingness and ability to comply with scheduled visits, treatment plan, laboratorytests and other study procedures

Exclusion Criteria:

• Current participation in another therapeutic clinical trial

• Symptomatic brain metastases

• History of previous cancer (non RMS), except squamous cell or basal-cell carcinomaof the skin or any in situ carcinoma that has been completely resected, whichrequired therapy within the previous 3 years. Other low grade cancers can bereviewed and allowed at the discretion of the PI

• Incomplete recovery from any surgery (other than central venous catheter or portplacement) prior to treatment

• Any of the following in the past 6 months: pericarditis, pericardial effusion,symptomatic congestive heart failure, cerebrovascular accident or transient ischemicattack, pulmonary embolism, deep vein thrombosis, symptomatic bradycardia,requirement for anti-arrhythmic medication

• History of prolonged corrected QT (QTc) interval (e.g., repeated demonstration of aQTc interval > 450 milliseconds, unless associated with the use of medications knownto prolong the QTc interval). QTc will be calculated using the Bazett formula (RRinterval = 60/heart rate; QTI corrected = QT interval/sqr[RRinterval])

• History of additional risk factors for torsade de pointes (e.g., heart failure,family history of long QT syndrome)

• Use of concomitant medications that increase or possibly increase the risk toprolong the QTc interval and/or induce torsades de pointes ventricular arrhythmia

• Females who are breastfeeding/lactating

• Known active infections (e.g., bacterial, fungal, viral including hepatitis andhuman immunodeficiency virus [HIV] positivity)

• Other severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase the risk associated with study participation or studydrug administration or may interfere with the interpretation of study results and,in the judgment of the investigator, would make the subject inappropriate for entryinto this study or compromise protocol objectives in the opinion of the investigatorand/or the sponsor