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

Sponsor

Washington University School of Medicine (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05826015

Collaborator

National Cancer Institute (NCI) (NIH), Aravive, Inc. (Industry)

Enrollment

Locations

Arm

114.2

Anticipated Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Recurrent High Grade Uterine Cancer	Drug: Paclitaxel Drug: Batiraxcept	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I/IB of AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer

Anticipated Study Start Date :

Jul 31, 2023

Anticipated Primary Completion Date :

Mar 3, 2028

Anticipated Study Completion Date :

Feb 4, 2033

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Paclitaxel + AVB-500 -Patients will receive up to nine 21-day cycles of paclitaxel + AVB-500. Patients will be receive AVB-500 via intravenous infusion at the assigned dose level on days 1, 8, and 15 of each cycle. Patients will receive intravenous paclitaxel at a dose of 175 mg/m^2 on day 1 of each cycle. If patients experience an allergic reaction to paclitaxel then docetaxel may be given at a dose of 75 mg/m^2 on day 1 of each cycle.	Drug: Paclitaxel IV over 3 hours Other Names: Taxol Drug: Batiraxcept IV over 60 minutes Other Names: AVB-500

Arm

Intervention/Treatment

Experimental: Paclitaxel + AVB-500

-Patients will receive up to nine 21-day cycles of paclitaxel + AVB-500. Patients will be receive AVB-500 via intravenous infusion at the assigned dose level on days 1, 8, and 15 of each cycle. Patients will receive intravenous paclitaxel at a dose of 175 mg/m^2 on day 1 of each cycle. If patients experience an allergic reaction to paclitaxel then docetaxel may be given at a dose of 75 mg/m^2 on day 1 of each cycle.

Drug: Paclitaxel

IV over 3 hours

Other Names:

Taxol

Drug: Batiraxcept

IV over 60 minutes

Other Names:

AVB-500

Outcome Measures

Primary Outcome Measures

Frequency and severity of treatment-related adverse events [From start of treatment though 30 days after the last dose of AVB-500 (estimated to be 31 weeks)]
-Graded by CTCAE v.5.

Secondary Outcome Measures

Serum sAXL and GAS6 ratio [At baseline]
Pharmacokinetic (PK) parameters (including Cmax) as determined from AVB-500 serum levels [Cycle 1 Day 1 pre-infusion, Cycle 1 Day 1 post-infusion, Cycle 1 Day 15 pre-infusion, and subsequent cycles day 1 pre-infusions (each cycle is 21 days)]
Pharmacokinetic (PK) parameters (including Tmax) as determined from AVB-500 serum levels [Cycle 1 Day 1 pre-infusion, Cycle 1 Day 1 post-infusion, Cycle 1 Day 15 pre-infusion, and subsequent cycles day 1 pre-infusions (each cycle is 21 days)]
Pharmacodynamic effects as determined by changes from baseline in serum GAS6 levels [Cycle 1 Day 1 pre-infusion, Cycle 1 Day 1 post-infusion, Cycle 1 Day 15 pre-infusion, and subsequent cycles day 1 pre-infusions (each cycle is 21 days)]
Overall response rate (ORR) [At completion of 3 cycles (cycle=21 days) (estimated to be 63 days)]
-Defined as the proportion of subjects who have a partial or complete response to therapy
Progression-free survival (PFS) [Through completion of follow-up (estimated to be 5 years and 27 weeks)]
-Defined as the time from start of treatment to the first radiologically documented disease progression, or death, whichever comes first. The alive patients without radiologically documented disease progression are censored at the last follow-up.
Recommended Phase 2 dose (RP2D) of AVB-500 in combination with paclitaxel [Through completion of cycle 1 (cycle=21 days) for all patients (estimated to be 48 months and 3 weeks)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143
2	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
3	University of New Mexico	Albuquerque	New Mexico	United States	87106
4	University of Oklahoma	Oklahoma City	Oklahoma	United States	73104