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

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

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.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer
• Intervention / Treatment: Other: Placebo; Drug: AVB-S6-500; Drug: Pegylated liposomal doxorubicin (PLD); Drug: Paclitaxel (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.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Arizona Oncology
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates
  • California
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland
    • Roseville, California, United States, 95661
      • Kaiser Permanente Roseville
    • San Francisco, California, United States, 94115
      • Kaiser Permanente San Francisco
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Santa Clara
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente Walnut Creek
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02214
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OUHSC-Stephenson Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute and Research Center
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology - Austin Central
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology - Fort Worth
    • San Antonio, Texas, United States, 78240
      • Texas Oncology - San Antonio Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Phase 1b: AVB-S6-500+PLD	Drug: AVB-S6-500; AVB-S6-500 is experimental drug; Drug: Pegylated liposomal doxorubicin (PLD); PLD is active comparator; Other Names: Doxil
EXPERIMENTAL: Phase 1b: AVB-S6-500+Pac	Drug: AVB-S6-500; AVB-S6-500 is experimental drug; Drug: Paclitaxel (Pac); Paclitaxel is active comparator; Other Names: Taxol
EXPERIMENTAL: Phase 2: AVB-S6-500+PLD	Drug: AVB-S6-500; AVB-S6-500 is experimental drug; Drug: Pegylated liposomal doxorubicin (PLD); PLD is active comparator; Other Names: Doxil
EXPERIMENTAL: Phase 2: AVB-S6-500+Pac	Drug: AVB-S6-500; AVB-S6-500 is experimental drug; Drug: Paclitaxel (Pac); Paclitaxel is active comparator; Other Names: Taxol
ACTIVE_COMPARATOR: Phase 2: Placebo+PLD	Other: Placebo; Placebo comparator; Drug: Pegylated liposomal doxorubicin (PLD); PLD is active comparator; Other Names: Doxil
ACTIVE_COMPARATOR: Phase 2: Placebo+Pac	Other: Placebo; Placebo comparator; Drug: Paclitaxel (Pac); Paclitaxel is active comparator; Other Names: Taxol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Measured by the number of patients with AEs in Phase 1 portion of the study.	6 months
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.	18 months
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.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: AUC	Area under the AVB-S6-500 concentration-time curve.	18 months
Pharmacokinetics: Cmax	Maximum observed AVB-S6-500 concentration.	18 months
Pharmacokinetics: Tmax	Time of maximum observed AVB-S6-500 concentration.	18 months
Pharmacokinetics: t1/2	Apparent terminal half-life of AVB-S6-500.	18 months
Pharmacodynamic marker assessment	Change from the baseline in GAS6 serum levels.	18 months
Anti-drug antibody (ADA) titers	Change from baseline in ADA titer.	18 months
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.	18 months
Disease control rate	Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.	18 months
Duration of response (DOR)	Measured from the date of partial or complete response to therapy until the cancer progresses.	18 months
Overall survival	Time following the treatment until death.	30 months
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.	18 months
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).	18 months

Collaborators and Investigators

• Sponsor: Aravive, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 6, 2018
• Primary Completion (ACTUAL): January 8, 2021
• Study Completion (ACTUAL): December 30, 2022

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: August 17, 2018
• First Posted (ACTUAL): August 21, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2023
• Last Update Submitted That Met QC Criteria: February 10, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Ovarian cancer; Platinum resistant
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: AVB500-OC-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No