SARC046: A Phase II Trial of Nab-Sirolimus in Patients With Progressing or Symptomatic Epithelioid Hemangioendothelioma
This is a non-randomized, open label, single arm Phase II trial with a two-stage design with histologically-confirmed metastatic and/or recurrent epithelioid hemangioendothelioma requiring systemic treatment. nab-Sirolimus 100 mg/m2 will be administered as an intravenous infusion over 30 minutes on Days 1 and 8 of each 21-day cycle. The primary objective is to determine ORR by RECIST v1.1 of nab-sirolimus in patients with EHE who require systemic treatment.
• Participants must have histologically or cytologically confirmed EHE that is either progressing 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 one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
• 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 related hypothyroidism). Toxicities that are permanent, like hearing loss from platinum agents, may be allowed if agreed to by the medical monitor.
• The effects of nab-sirolimus on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of nab-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 consent document. (Providing consents in as many languages as possible is encouraged).