A Phase I Trial of Zanzalintinib Combined With Eribulin in Advanced Liposarcoma and Leiomyosarcoma
The investigators hypothesize that the combination of eribulin and zanzalintinib will be tolerable and lead to improved progression-free survival (PFS) as compared to eribulin alone based on historical data.
• Pathologically proven diagnosis of unresectable or metastatic leiomyosarcoma or adipocytic sarcoma.
• Progressed on at least 1 line of prior therapy and have received no more than 4 lines of prior therapy.
• Measurable disease per RECIST 1.1.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Adequate bone marrow and organ function within 14 days before first dose of study treatment as defined below:
‣ Absolute neutrophil count ≥ 1.5 K/cumm without granulocyte colony-stimulating factor support within 2 weeks of collection
⁃ Platelets ≥ 100 K/cumm without transfusion within 2 weeks of collection
⁃ Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks of collection
⁃ INR ≤ 1.5 x ULN and aPTT ≤ 1.2 x ULN; for subjects on Factor Xa inhibitors, this criterion does not apply.
⁃ Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease, ≤ 3.0 x IULN)
⁃ AST(SGOT)/ALT(SGPT)/alkaline phosphatase (ALP) ≤ 3.0 x IULN (for subjects with documented bone metastasis, ALP ≤ 5.0 x IULN)
⁃ Serum albumin ≥ 2.8 g/dL
⁃ Serum creatine ≤ 1.5 x IULN or calculated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault
⁃ UPCR ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine
• Recovery to baseline or ≤ grade 1 from AEs, including immune-related AEs related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy (e.g., physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ grade 2 hypomagnesemia, ≤ grade 2 neuropathy are permitted.
• The effects of zanzalintinib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 186 days after last dose of zanzalintinib (for women) or 96 days after last dose of zanzalintinib (for men). Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.