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Efficacy and Safety Study of AVB-S6-500 in Patients With Platinum-Resistant Recurrent Ovarian Cancer

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AVB-S6-500
Paclitaxel (Pac)
Pegylated liposomal doxorubicin (PLD)
Placebo
Sponsored by
Aravive, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian cancer, Platinum resistant

Eligibility Criteria

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

Inclusion Criteria:

  • Age 18 years or older
  • Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal cancer.
  • Platinum resistant disease, defined as progression within ≤ 6 months from completion of most recent regimen and calculated from the date of the last administered dose of platinum therapy
  • Must have available archived tumor tissue OR if archived tissue is not available, willing to provide a fresh tumor biopsy
  • Must have radiologic imaging with a computerized tomography (CT) scan or magnetic resonance imaging (MRI) within 4 weeks of first dose of study drug
  • Received at least 1 but not more than 3 therapy regimens, not including maintenance or adjuvant therapy
  • Must have ovarian cancer that is measurable according to RECIST 1.1
  • ECOG performance status of 0-1
  • Normal gastrointestinal (GI), bone marrow, liver and kidney function
  • At least 28 days between termination of prior anti-cancer or hormonal therapy and administration of AVB-S6-500

Exclusion Criteria:

  • Primary platinum-refractory disease (defined as progression during the first platinum regimen or within 4 weeks of completion of the first platinum regimen)
  • Currently being treated with concurrent anti-cancer therapy or any other interventional treatment or trial
  • Received prior therapy with Pac or PLD in the recurrent setting, depending on physician-chosen chemotherapy for this study
  • Significant cardiac disease history
  • Has other prior or concurrent malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • Symptomatic CNS metastasis or metastases
  • Serious active infection requiring IV antibiotics and/or hospitalization at study entry
  • Has known previous or current human immune deficiency (HIV) syndrome, hepatitis B, or hepatitis C
  • Has had paracentesis for ascites within 3 months

Sites / Locations

  • Arizona Oncology
  • Arizona Oncology Associates
  • Kaiser Permanente Oakland
  • Kaiser Permanente Roseville
  • Kaiser Permanente San Francisco
  • Kaiser Permanente Santa Clara
  • Kaiser Permanente Vallejo
  • Kaiser Permanente Walnut Creek
  • Massachusetts General Hospital
  • Dana Farber Cancer Institute
  • Washington University
  • OUHSC-Stephenson Cancer Center
  • Willamette Valley Cancer Institute and Research Center
  • Texas Oncology - Austin Central
  • Texas Oncology - Fort Worth
  • Texas Oncology - San Antonio Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

Phase 1b: AVB-S6-500+PLD

Phase 1b: AVB-S6-500+Pac

Phase 2: AVB-S6-500+PLD

Phase 2: AVB-S6-500+Pac

Phase 2: Placebo+PLD

Phase 2: Placebo+Pac

Arm Description

Outcomes

Primary Outcome Measures

Incidence of Adverse Events (AEs)
Measured by the number of patients with AEs in Phase 1 portion of the study.
Anti-tumor activity of AVB-S6-500 in combination with PLD
Measured by progression free survival (PFS) in patients receiving AVB-S6-500+PLD versus patients receiving Placebo+PLD in Phase 2 portion of the study.
Anti-tumor activity of AVB-S6-500 in combination with Pac
Measured by progression free survival (PFS) in patients receiving AVB-S6-500+ Pac versus patients receiving Placebo+Pac in Phase 2 portion of the study.

Secondary Outcome Measures

Pharmacokinetics: AUC
Area under the AVB-S6-500 concentration-time curve.
Pharmacokinetics: Cmax
Maximum observed AVB-S6-500 concentration.
Pharmacokinetics: Tmax
Time of maximum observed AVB-S6-500 concentration.
Pharmacokinetics: t1/2
Apparent terminal half-life of AVB-S6-500.
Pharmacodynamic marker assessment
Change from the baseline in GAS6 serum levels.
Anti-drug antibody (ADA) titers
Change from baseline in ADA titer.
Objective response rate
Proportion of subjects who have a partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as well as Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)-125 criteria.
Disease control rate
Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
Duration of response (DOR)
Measured from the date of partial or complete response to therapy until the cancer progresses.
Overall survival
Time following the treatment until death.
CA-125 response rate
Proportion of subjects with a minimum 50% reduction in CA-125 serum levels lasting for 28 days relative to baseline CA-125 serum levels.
Quality of Life(QOL)
Subject QOL will be assessed every 8 weeks during treatment using the Functional Assessment Of Cancer Therapy - Ovarian Cancer (FACT-O) questionnaire, which consists of 4 subscales: physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), and functional well-being (7 questions), and 12 additional concerns specific to ovarian cancer. All items are rated on a 5 point scale with 0 "not at all" and 4 "very much". The scoring algorithm allows for eight summary scales: the four core well-being subscales, a subtotal of the 27 core items, a subtotal of the 12 ovarian-specific additional concerns, a grand total of the 39 items, and a trial outcome index (sum of the 17 physical and functional wellbeing items plus the 12 ovarian-specific items).

Full Information

First Posted
August 17, 2018
Last Updated
February 10, 2023
Sponsor
Aravive, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT03639246
Brief Title
Efficacy and Safety Study of AVB-S6-500 in Patients With Platinum-Resistant Recurrent Ovarian Cancer
Official Title
A Phase 1b/2 Randomized, Controlled Study of AVB-S6-500 in Combination With Pegylated Liposomal Doxorubicin (PLD) or Paclitaxel (Pac) in Patients With Platinum-resistant Recurrent Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
December 6, 2018 (Actual)
Primary Completion Date
January 8, 2021 (Actual)
Study Completion Date
December 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Aravive, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a Phase 1b/2 study of AVB-S6-500 in combination with pegylated liposomal doxorubicin (PLD) or paclitaxel (Pac) in patients with platinum resistant recurrent ovarian cancer. The phase 1b portion of the study is open label and patients will receive either AVB-S6-500+PLD or AVB-S6-500+ Pac. The Phase 2 portion of the study is randomized, double-blind, placebo-controlled study to compare efficacy and tolerability of AVB-S6-500 in combination with PLD or Pac versus placebo plus PLD or Pac.
Detailed Description
While this study was planned as two-part study consisting of a Phase 1b and a Phase 2 portion, the sponsor decided not to proceed with the Phase 2 portion. The Phase 1b portion of the study was a multicenter, 2-group, open-label design to evaluate the safety and tolerability of AVB-S6-500 combined with PLD or Pac in subjects with platinum-resistant recurrent ovarian cancer. The decision to enroll in the Phase 2 portion of the study was to be driven by the recommendation of a safe and tolerable dose of AVB-S6-500 in combination with each chemotherapy backbone; however, enrollment into the Phase 2 portion was not initiated per Sponsor decision. Given that sufficient data were obtained in the Phase 1b portion AVB-S6-500 + Pac group, the decision was made to pursue a randomized Phase 3 to further study the benefit of this combination versus paclitaxel alone in patients with platinum resistant ovarian cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
Ovarian cancer, Platinum resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
53 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase 1b: AVB-S6-500+PLD
Arm Type
Experimental
Arm Title
Phase 1b: AVB-S6-500+Pac
Arm Type
Experimental
Arm Title
Phase 2: AVB-S6-500+PLD
Arm Type
Experimental
Arm Title
Phase 2: AVB-S6-500+Pac
Arm Type
Experimental
Arm Title
Phase 2: Placebo+PLD
Arm Type
Active Comparator
Arm Title
Phase 2: Placebo+Pac
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
AVB-S6-500
Intervention Description
AVB-S6-500 is experimental drug
Intervention Type
Drug
Intervention Name(s)
Paclitaxel (Pac)
Other Intervention Name(s)
Taxol
Intervention Description
Paclitaxel is active comparator
Intervention Type
Drug
Intervention Name(s)
Pegylated liposomal doxorubicin (PLD)
Other Intervention Name(s)
Doxil
Intervention Description
PLD is active comparator
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo comparator
Primary Outcome Measure Information:
Title
Incidence of Adverse Events (AEs)
Description
Measured by the number of patients with AEs in Phase 1 portion of the study.
Time Frame
6 months
Title
Anti-tumor activity of AVB-S6-500 in combination with PLD
Description
Measured by progression free survival (PFS) in patients receiving AVB-S6-500+PLD versus patients receiving Placebo+PLD in Phase 2 portion of the study.
Time Frame
18 months
Title
Anti-tumor activity of AVB-S6-500 in combination with Pac
Description
Measured by progression free survival (PFS) in patients receiving AVB-S6-500+ Pac versus patients receiving Placebo+Pac in Phase 2 portion of the study.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Pharmacokinetics: AUC
Description
Area under the AVB-S6-500 concentration-time curve.
Time Frame
18 months
Title
Pharmacokinetics: Cmax
Description
Maximum observed AVB-S6-500 concentration.
Time Frame
18 months
Title
Pharmacokinetics: Tmax
Description
Time of maximum observed AVB-S6-500 concentration.
Time Frame
18 months
Title
Pharmacokinetics: t1/2
Description
Apparent terminal half-life of AVB-S6-500.
Time Frame
18 months
Title
Pharmacodynamic marker assessment
Description
Change from the baseline in GAS6 serum levels.
Time Frame
18 months
Title
Anti-drug antibody (ADA) titers
Description
Change from baseline in ADA titer.
Time Frame
18 months
Title
Objective response rate
Description
Proportion of subjects who have a partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as well as Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)-125 criteria.
Time Frame
18 months
Title
Disease control rate
Description
Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
Time Frame
18 months
Title
Duration of response (DOR)
Description
Measured from the date of partial or complete response to therapy until the cancer progresses.
Time Frame
18 months
Title
Overall survival
Description
Time following the treatment until death.
Time Frame
30 months
Title
CA-125 response rate
Description
Proportion of subjects with a minimum 50% reduction in CA-125 serum levels lasting for 28 days relative to baseline CA-125 serum levels.
Time Frame
18 months
Title
Quality of Life(QOL)
Description
Subject QOL will be assessed every 8 weeks during treatment using the Functional Assessment Of Cancer Therapy - Ovarian Cancer (FACT-O) questionnaire, which consists of 4 subscales: physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), and functional well-being (7 questions), and 12 additional concerns specific to ovarian cancer. All items are rated on a 5 point scale with 0 "not at all" and 4 "very much". The scoring algorithm allows for eight summary scales: the four core well-being subscales, a subtotal of the 27 core items, a subtotal of the 12 ovarian-specific additional concerns, a grand total of the 39 items, and a trial outcome index (sum of the 17 physical and functional wellbeing items plus the 12 ovarian-specific items).
Time Frame
18 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years or older Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal cancer. Platinum resistant disease, defined as progression within ≤ 6 months from completion of most recent regimen and calculated from the date of the last administered dose of platinum therapy Must have available archived tumor tissue OR if archived tissue is not available, willing to provide a fresh tumor biopsy Must have radiologic imaging with a computerized tomography (CT) scan or magnetic resonance imaging (MRI) within 4 weeks of first dose of study drug Received at least 1 but not more than 3 therapy regimens, not including maintenance or adjuvant therapy Must have ovarian cancer that is measurable according to RECIST 1.1 ECOG performance status of 0-1 Normal gastrointestinal (GI), bone marrow, liver and kidney function At least 28 days between termination of prior anti-cancer or hormonal therapy and administration of AVB-S6-500 Exclusion Criteria: Primary platinum-refractory disease (defined as progression during the first platinum regimen or within 4 weeks of completion of the first platinum regimen) Currently being treated with concurrent anti-cancer therapy or any other interventional treatment or trial Received prior therapy with Pac or PLD in the recurrent setting, depending on physician-chosen chemotherapy for this study Significant cardiac disease history Has other prior or concurrent malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix Symptomatic CNS metastasis or metastases Serious active infection requiring IV antibiotics and/or hospitalization at study entry Has known previous or current human immune deficiency (HIV) syndrome, hepatitis B, or hepatitis C Has had paracentesis for ascites within 3 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Franke
Organizational Affiliation
Aravive, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Oncology
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Arizona Oncology Associates
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85711
Country
United States
Facility Name
Kaiser Permanente Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94611
Country
United States
Facility Name
Kaiser Permanente Roseville
City
Roseville
State/Province
California
ZIP/Postal Code
95661
Country
United States
Facility Name
Kaiser Permanente San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Facility Name
Kaiser Permanente Santa Clara
City
Santa Clara
State/Province
California
ZIP/Postal Code
95051
Country
United States
Facility Name
Kaiser Permanente Vallejo
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
Kaiser Permanente Walnut Creek
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94596
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02214
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
OUHSC-Stephenson Cancer Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Eugene
State/Province
Oregon
ZIP/Postal Code
97401
Country
United States
Facility Name
Texas Oncology - Austin Central
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Facility Name
Texas Oncology - Fort Worth
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Oncology - San Antonio Medical Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78240
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Efficacy and Safety Study of AVB-S6-500 in Patients With Platinum-Resistant Recurrent Ovarian Cancer

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