Metastatic Olfactory Neuroblastoma
Conditions
Brief summary
The goal of this clinical research study is to learn if zanzalintinib can help to control recurrent/metastatic ONB. The safety of zanzalintinib will also be studied.
Detailed description
Primary Objectives: • To assess the efficacy of Zanzalintinib in patients with R/M ONB Endpoint ORR, defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) as measured by response evaluation criteria in solid tumors (RECIST), version 1.1, as determined by investigator radiologist assessment. Secondary Objectives: • To assess the metabolic response of Zanzalintinib in patients with R/M ONB Endpoint Objective Metabolic Response Rate (OMRR), defined as the proportion of patients who achieve a complete metabolic response (CMR) or partial metabolic response (PMR), as measured by PERCIST v.1.0 using DOTATATE-PET imaging, based on investigator assessment by radiology and/or nuclear medicine. • To estimate the median duration of response (DOR) Endpoint DOR, defined as time from first documentation of CR or PR to the earliest date of documented disease progression or death from any cause, or last follow-up without disease progression or death, whichever occurs first. • Duration of metabolic response (DOMR) Endpoint DOMR, defined as time from first documentation of CMR or PMR to the earliest date of documented metabolic disease progression or death from any cause, or last follow-up without disease progression or death, whichever occurs first. • Time to response Endpoint Among objective responders (CR and PR), the time between the date treatment was started (C1D1) and first radiological evidence of CR or PR. • To estimate the median progression-free survival (PFS) and 12-months PFS rate Endpoint PFS, defined as the time from the date of dose initiation to the earliest date of documented disease progression, or death from any cause, or last follow-up without disease progression or death, whichever occurs first. To estimate the median overall survival (OS) and 12-months OS Endpoint OS, defined as time from date of dose initiation to death from any cause or last follow-up without death. • To assess safety of Zanzalintinib Endpoint Safety will be measured as the incidence of adverse events (AEs) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. Tertiary/Exploratory Objectives • To explore biomarkers that may predict response to therapy Endpoint Correlation of clinical response with biomarkers at baseline and/or on treatment. Correlatives analysis may include, but are not limited to, genomic (tumor molecular profiling, RNAseq) and proteomics (mIF or IMC) profiling.
Interventions
DRUGZanzalintinib
Given orally
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
All subjects must meet all the following inclusion criteria to be eligible for participation in this study: 1. Subjects ≥18 years with histology-proven R/M ONB. 2. Not amenable to curative intent surgery or radiotherapy 3. Measurable disease per RECIST 1.1 4. Performance status ECOG of 0 or 1 5. VEGFR-inhibitor naïve (R/M ONB never treated with VEGFR inhibitors including Zanzalintinib) 6. Adequate organ and marrow function, based upon meeting all the following laboratory criteria within 14 days before first dose of study treatment 1. Hemoglobin ≥ 9 g/dL without transfusion within 2 weeks prior to screening laboratory sample collection. 2. Absolute neutrophil count ≥ 1500/mm3 (≥ 1.5 GI/L) without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection. 3. Platelets ≥ 100 x 109/mL without transfusion within 2 weeks of screening laboratory sample collection. 7. Laboratory measurements, renal function: 1. Creatinine clearance ≥ 40 mL/min as assessed by the Cockcroft-Gault equation 2. Urine protein creatinine ration (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol creatinine) 8. Laboratory measurements, hepatic function: 1. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN. For subjects with CRPC and bone metastasis ALP ≤ 10 x ULN if predominantly bone-specific ALP. 2. Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN ). 3. International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN ). 9. Sexually active fertile subjects and their partners must agree to use highly effective method of contraception (defined in Appendix A) during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods. a. Through 186 days after the last dose of zanzalintinib for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib for men 10. Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating hormone \[FSH\] level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. 11. Capable of understanding and complying with protocol requirement and must have signed informed consent.
Exclusion criteria
All Patients Patients who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Adverse Events (AEs) | Through study completion; an average of 1 year | Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0 |
Countries
United States
Contacts
CONTACTLuana Sousa, MD
PRINCIPAL_INVESTIGATORLuana Sousa, MD
UT MD Anderson
Outcome results
None listed