AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer

• Status: Not yet recruiting
• Trial end date: 2033-02-04
• Target enrollment: 0
• Participant gender: Female

Summary

The investigators propose a Phase I/IB trial for patients with advanced stage, uterine serous or high grade endometrioid tumors. The trial will include a dose escalation phase of 6-24 patients to define the maximum tolerated dose of AVB-500 in combination with standard-of-care paclitaxel. The trial will also include a dose expansion phase of 12 patients. Additionally, all patients will be consented and approached for 13C-glucose (13C is a stable, non-radioactive isotope) infusion before biopsy for metabolomic assays. Tumors and biopsies will be assessed by immunohistochemistry to identify potential biomarkers of response.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborators: Aravive, Inc.; National Cancer Institute (NCI)
• Treatments: Paclitaxel

Criteria

Inclusion Criteria:

• Diagnosis of FIGO grade 3 endometrioid, serous, or mixed recurrent high grade uterine or endometrial cancer

• Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective.

• Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest x-ray, or >10 mm with calipers by clinical exam by RECIST 1.1.

• Women or transgender men with a uterus who are at least 18 years of age.

• ECOG performance status ≤ 2

• Normal bone marrow and organ function as defined below:

• Absolute neutrophil count ≥ 1,500/mcl

• Platelets ≥ 100,000/mcl

• Hemoglobin ≥ 9.0 g/dL

• Total bilirubin ≤ 1.5 x IULN

• AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (unless liver metastases are present in which case AST/ALT must be ≤ 5.0 x IULN)

• Serum creatinine < 2.0 mg/dL or < 177 µmol/L OR calculated or measured creatinine clearance ≥ 40 mL/min (using Cockcroft-Gault equation)

• INR ≤ 1.5 x IULN

• aPTT ≤ 1.5 x IULN

• The effects of AVB-500 on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, patients of childbearing potential 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 patient become pregnant or suspect pregnancy while participating in this study, the treating physician must be informed immediately.

• Women who received prior treatment with trastuzumab can enroll in the study

• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

• Any prior treatment with AVB-500

• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.

• Currently receiving any other (non-study) cytotoxic chemotherapy.

• Currently receiving any other investigational agents or has received an investigational agent within 4 weeks of start of study treatment.

• Known brain metastases. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to AVB-500 or other agents used in the study.

• Abnormal gastrointestinal function, defined as Grade >2 diarrhea, constipation, nausea, vomiting, or abdominal pain. This includes GI obstruction or bleeding or signs/symptoms thereof within 3 months of study enrollment. Patients with a history of abdominal fistula will be considered eligible if the fistula was surgically repaired or has healed, there has been no evidence of fistula for at least 6 months, and patient is deemed to be at low risk of recurrent fistula.

• Significant cardiac disease history including:

• Clinically significant atrial or ventricular arrhythmias requiring treatment

• Medically controlled congestive heart failure

• Significant angina or clinically and/or electrocardiographically documented myocardial infarction within the past year

• Clinically significant valvular disease

• Non-healing wound, ulcer, or bone fracture.

• Known active hepatitis; ongoing systemic bacterial, fungal, or viral infection; known HIV infection or AIDS-related illness.

• History or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, or history of CVA, TIA, or subarachnoid hemorrhage within 6 months of the first date of treatment on this study.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

• History of major surgical procedure within 14 days prior to start of study treatment.

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.