SARC046: A Phase II Trial of Nab-Sirolimus in Patients With Progressing or Symptomatic Epithelioid Hemangioendothelioma

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed EHE that is eitherprogressing or clinically symptomatic, not a candidate for curative intent surgery,and requires systemic therapy in the opinion of the investigator.

• Participants must have measurable disease by RECIST v1.1, defined as at least onelesion that can be accurately measured in at least one dimension (longest diameterto be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinicalexam. See Section 12 (Measurement of Effect) for the evaluation of measurabledisease.

• Age ≥18 years

• ECOG performance status ≤2

• Participants must meet the following organ and marrow function as defined below:

• Platelets >75,000μl

• ANC >1500μl

• Hgb >9g/dl

• Creatinine <1.5 x ULN or measured CrCl of >30ml/m2/1.73 m2

• Total bilirubin <2 x ULN

• AST/ALT <3 x ULN

• Patients must have recovered from toxicity related to prior therapy to grade <=1 (defined by CTCAE v5.0) (except alopecia and neuropathy, or immunotherapy relatedhypothyroidism). Toxicities that are permanent, like hearing loss from platinumagents, may be allowed if agreed to by the medical monitor.

• The effects of nab-sirolimus on the developing human fetus are unknown. For thisreason, women of child-bearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior tostudy entry and for the duration of study participation. Should a woman becomepregnant or suspect she is pregnant while she or her partner is participating inthis study, she should inform her treating physician immediately. Men treated orenrolled on this protocol must also agree to use adequate contraception prior to thestudy, for the duration of study participation, and 4 months after completion ofnab-sirolimus administration.

• Female patient of childbearing potential has a negative serum pregnancy test within 7 days of study enrollment.

• Ability to understand and the willingness to sign a written informed consentdocument. (Providing consents in as many languages as possible is encouraged).

Exclusion Criteria:

• Patient with current evidence of active and uncontrolled infection, NYHA ClassIII-IV CHF, documented Child's class B-C cirrhosis, or uncontrolled medical diseasewhich in the opinion of the investigator or the sponsor could compromise safetyand/or assessment of efficacy.

• Active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjectswho are positive for hepatitis B core antibody, hepatitis B surface antigen, orhepatitis C antibody must have a negative PCR result before enrollment; those whoare PCR positive will be excluded. HIV+ patients are allowed provided the patienthas a CD4 count greater than 200 and is HIV undetectable on antiviral medications,and there are no AIDS-defining illnesses within 12 months. The antiviral medicationregimen must not contain a strong CYP3A4 inhibitor (eg protease inhibitors).

• Major surgical procedure or open surgical biopsy within 28 days of first dose ofstudy drug

• Active central nervous system (CNS) disease involvement, or prior history of NCICTCAE Grade ≥3 drug-related CNS toxicity. Subjects with known CNS metastases thatare treated and stable (without evidence of CNS toxicity) and are not requiringsystemic steroids are allowed to be enrolled.

• Patient has known psychiatric or substance abuse disorders that would interfere withcooperation with the requirements of the trial.

• Myocardial infarction within 12 months of screening

• Co-existing malignancies or use of any other concurrent investigational agents oranticancer agents, excluding adjuvant hormonal therapy for breast or prostatecancer.

• Pregnant women are excluded from this study because there is an unknown butpotential risk for adverse events in nursing infants secondary to treatment of themother with nab-sirolimus, breastfeeding should be discontinued if the mother istreated with nab-sirolimus.