A Phase II Study of Rivoceranib for Patients With Recurrent or Metastatic Olfactory Neuroblastoma

Exclusion Criteria

• •1. Prior radiation therapy (or other nonsystemic therapy) within 2 weeks prior to enrollment
• •2. Active CNS disease (participants with asymptomatic and stable, treated CNS lesions who have been off corticosteroids, radiation, or other CNS-directed therapy for at least 4 weeks are not considered active)
• •3. Red blood cell transfusion dependence, defined as requiring more than 2 units of packed red blood cell transfusions during the 4-week period prior to screening. Red blood cell transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criterion.
• •4. Prior anticancer therapy including, but not limited to, chemotherapy, immunotherapy, or investigational agents within 4 weeks or 5 half-lives prior to rivoceranib treatment
• •5. Current participation in another interventional clinical study
• •6. History of previous malignancy other than malignancy treated with curative intent within less than 5 years. Participants with the following diagnoses represents an exception and may enroll if ≥ 1 year with no evidence of active disease before the first dose of the study drug.:
• •1. Non-melanoma skin cancers with no current evidence of disease
• •2. Melanoma in situ with no current evidence of disease
• •3. Localized cancer of the prostate with prostate-specific antigen of \<1 ng/mL
• •4. Treated or localized well-differentiated thyroid cancer
• •5. Treated cervical carcinoma in situ
• •6. Treated ductal/lobular carcinoma in situ of the breast
• •7. Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤ 10 days prior to administration of investigational product. Participants with known hepatitis B, hepatitis C (HCV), or HIV infection could go on study provided the viral load is undetectable at screening.
• •8. Participants with poor-controlled arterial hypertension (systolic blood pressure \> 140 mmHg and diastolic blood pressure \> 90 mmHg) despite standard medical management
• •9. Participants with Grade II or greater myocardial ischemia or myocardial infarction, uncontrolled arrhythmias (QTc interval ≥ 450 ms in males and ≥ 470 ms in females);
• •10. Participants with NYHA (see Appendix 5) Class III-IV cardiac insufficiency or LVEF (left ventricular ejection fraction) \< 50% by echocardiography;
• •11. Presence of multiple factors affecting oral medications (such as inability to swallow, chronic diarrhea, and intestinal obstruction, which significantly affect drug administration and absorption);
• •12. Urine protein ≥ ++ or 24 h urine protein \> 1.0 g as indicated by urinalysis
• •13. Female subjects who are pregnant or breast-feeding
• •14. Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient