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

NCT05826015 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 202306082
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to determine safety and tolerability of AVB-500 when given in combination with paclitaxel in patients with recurrent high-grade uterine cancer.

Conditions

Recurrent High Grade Uterine Cancer

Keywords

Batiraxcept; AVB-500; uterine serous; high-grade endometrioid; paclitaxel

Outcome Measures

Primary Outcomes (1)

• Frequency and severity of treatment-emergent adverse events

  -Graded by CTCAE v.5.

  From start of treatment though 30 days after the last dose of AVB-500 (estimated to be 31 weeks)

Secondary Outcomes (9)

• 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)

  Through completion of treatment (estimated to be 27 weeks)

Study Arms (1)

Paclitaxel + AVB-500

EXPERIMENTAL

Patients will receive up to 9 21-day cycles of paclitaxel + AVB-500. Patients will receive AVB-500 via intravenous (IV) infusion at the assigned dose level on days 1, 8, and 15 of each cycle. Patients will receive IV paclitaxel at a dose of 175 mg/m\^2 on day 1 of each cycle. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial response or stable disease will continue on treatment for another 3 cycles of paclitaxel + AVB-500 at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response (PR) or stable disease (SD). Up to 9 cycles of treatment with paclitaxel + AVB-500 may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance AVB-500 until progression. Patients with complete response will continue single agent AVB-500 as maintenance therapy until progression.

Drug: Paclitaxel; Drug: Batiraxcept

Interventions

Paclitaxel DRUG

IV over 3 hours

Also known as: Taxol

Paclitaxel + AVB-500

Batiraxcept DRUG

IV over 60 minutes

Also known as: AVB-500

Paclitaxel + AVB-500

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of recurrent, FIGO grade 3 endometrioid, serous, or mixed high grade uterine or endometrial cancer. Patients must have experienced either prior progression on a platinum-based therapy or intolerance to platinum. Patients with dMMR or MSI-H tumors or targetable HER2 alterations are required to have received prior therapy with appropriate targeted agents.
• Patients must have disease that cannot be managed by local therapy.
• Measurable disease 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 ≥ 1.5 K/cumm
• Platelets ≥ 100 K/cumm
• 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.

You may not qualify if:

• 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, radiation, targeted treatment, or immunotherapy within 4 weeks prior of start of study treatment.
• 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.
• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator
• Aravive, Inc.: collaborator

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Interventions

Paclitaxel; AVB-500 fusion protein

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• David G Mutch, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: April 24, 2023
• Study Start: October 31, 2024
• Primary Completion (Estimated): June 3, 2029
• Study Completion (Estimated): June 4, 2034
• Last Updated: October 2, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share