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

Primary Purpose

Recurrent High Grade Uterine Cancer

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Paclitaxel
Batiraxcept
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent High Grade Uterine Cancer focused on measuring Batiraxcept, AVB-500, uterine serous, high-grade endometrioid, paclitaxel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: 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. Subjects who have received prior treatment with trastuzumab, pembrolizumab, or dostarlimab 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, 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. 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. Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended. Recommend exclusion of specific ART agents based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates, concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers (efavirenz) should be contraindicated).

Sites / Locations

  • University of California, San Francisco
  • Washington University School of Medicine
  • University of New Mexico
  • University of Oklahoma

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Paclitaxel + AVB-500

Arm Description

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.

Outcomes

Primary Outcome Measures

Frequency and severity of treatment-emergent adverse events
-Graded by CTCAE v.5.

Secondary Outcome Measures

Serum sAXL and GAS6 ratio
Pharmacokinetic (PK) parameters (including Cmax) as determined from AVB-500 serum levels
Pharmacokinetic (PK) parameters (including Tmax) as determined from AVB-500 serum levels
Pharmacodynamic effects as determined by changes from baseline in serum GAS6 levels
Overall response rate (ORR)
-Defined as the proportion of subjects who have a partial or complete response to therapy
Progression-free survival (PFS)
-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
Incidence of anti-drug antibodies (ADA)
Overall survival (OS)
-Defined as the time from start of treatment to death. The alive patients are censored at the last follow-up.

Full Information

First Posted
April 11, 2023
Last Updated
August 1, 2023
Sponsor
Washington University School of Medicine
Collaborators
National Cancer Institute (NCI), Aravive, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05826015
Brief Title
AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer
Official Title
Phase I/IB of AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 30, 2023 (Anticipated)
Primary Completion Date
May 3, 2028 (Anticipated)
Study Completion Date
April 4, 2033 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Cancer Institute (NCI), Aravive, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent High Grade Uterine Cancer
Keywords
Batiraxcept, AVB-500, uterine serous, high-grade endometrioid, paclitaxel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Paclitaxel + AVB-500
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Taxol
Intervention Description
IV over 3 hours
Intervention Type
Drug
Intervention Name(s)
Batiraxcept
Other Intervention Name(s)
AVB-500
Intervention Description
IV over 60 minutes
Primary Outcome Measure Information:
Title
Frequency and severity of treatment-emergent adverse events
Description
-Graded by CTCAE v.5.
Time Frame
From start of treatment though 30 days after the last dose of AVB-500 (estimated to be 31 weeks)
Secondary Outcome Measure Information:
Title
Serum sAXL and GAS6 ratio
Time Frame
At baseline
Title
Pharmacokinetic (PK) parameters (including Cmax) as determined from AVB-500 serum levels
Time Frame
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)
Title
Pharmacokinetic (PK) parameters (including Tmax) as determined from AVB-500 serum levels
Time Frame
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)
Title
Pharmacodynamic effects as determined by changes from baseline in serum GAS6 levels
Time Frame
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)
Title
Overall response rate (ORR)
Description
-Defined as the proportion of subjects who have a partial or complete response to therapy
Time Frame
Through completion of treatment (estimated to be 27 weeks)
Title
Progression-free survival (PFS)
Description
-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.
Time Frame
Through completion of follow-up (estimated to be 5 years and 27 weeks)
Title
Recommended Phase 2 dose (RP2D) of AVB-500 in combination with paclitaxel
Time Frame
Through completion of cycle 1 (cycle=21 days) for all patients (estimated to be 48 months and 3 weeks)
Title
Incidence of anti-drug antibodies (ADA)
Time Frame
Day 1 of each cycle (cycle-21 days) and end of treatment (estimated to be 27 weeks)
Title
Overall survival (OS)
Description
-Defined as the time from start of treatment to death. The alive patients are censored at the last follow-up.
Time Frame
Through completion of follow-up (estimated to be 5 years and 27 weeks)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Subjects who have received prior treatment with trastuzumab, pembrolizumab, or dostarlimab 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, 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. 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. Patients with HIV are eligible unless their CD4+ T-cell counts are < 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended. Recommend exclusion of specific ART agents based on predicted drug-drug interactions (i.e. for sensitive CYP3A4 substrates, concurrent strong CYP3A4 inhibitors (ritonavir and cobicistat) or inducers (efavirenz) should be contraindicated).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David G Mutch, M.D.
Phone
314-362-3181
Email
mutchd@wustl.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David G Mutch, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Katherine Fuh, M.D., Ph.D.
Phone
415-885-5761
First Name & Middle Initial & Last Name & Degree
Katherine Fuh, M.D., Ph.D.
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David G Mutch, M.D.
Phone
314-362-3181
Email
mutchd@wustl.edu
First Name & Middle Initial & Last Name & Degree
David G Mutch, M.D.
First Name & Middle Initial & Last Name & Degree
Andrea R Hagemann, M.D.
First Name & Middle Initial & Last Name & Degree
Ian Hagemann, M.D.
First Name & Middle Initial & Last Name & Degree
Lindsay Kuroki, M.D.
First Name & Middle Initial & Last Name & Degree
L. Stewart Massad, M.D.
First Name & Middle Initial & Last Name & Degree
Carolyn McCourt, M.D.
First Name & Middle Initial & Last Name & Degree
Dineo Khabele, M.D.
First Name & Middle Initial & Last Name & Degree
Matthew A Powell, M.D.
First Name & Middle Initial & Last Name & Degree
Premal Thaker, M.D.
First Name & Middle Initial & Last Name & Degree
Maggie Mullen, M.D.
First Name & Middle Initial & Last Name & Degree
Esther Lu, Ph.D.
Facility Name
University of New Mexico
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolyn Muller, M.D.
Phone
505-272-2111
First Name & Middle Initial & Last Name & Degree
Carolyn Muller, M.D.
Facility Name
University of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathleen Moore, M.D.
Phone
405-271-8707
First Name & Middle Initial & Last Name & Degree
Kathleen Moore, M.D.

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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