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

• ClinicalTrials.gov Identifier: NCT03639246
• Recruitment Status: Completed
• First Posted: August 21, 2018
• Last Update Posted: February 13, 2023
• Sponsor: Aravive, Inc.
• Information provided by (Responsible Party): Aravive, Inc.

Tracking Information

• First Submitted Date: August 17, 2018
• First Posted Date: August 21, 2018
• Last Update Posted Date: February 13, 2023
• Actual Study Start Date: December 6, 2018
• Actual Primary Completion Date: January 8, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 17, 2018)

• Incidence of Adverse Events (AEs) [ Time Frame: 6 months ]
  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 [ Time Frame: 18 months ]
  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 [ Time Frame: 18 months ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 20, 2018)

• Pharmacokinetics: AUC [ Time Frame: 18 months ]
  Area under the AVB-S6-500 concentration-time curve.
• Pharmacokinetics: Cmax [ Time Frame: 18 months ]
  Maximum observed AVB-S6-500 concentration.
• Pharmacokinetics: Tmax [ Time Frame: 18 months ]
  Time of maximum observed AVB-S6-500 concentration.
• Pharmacokinetics: t1/2 [ Time Frame: 18 months ]
  Apparent terminal half-life of AVB-S6-500.
• Pharmacodynamic marker assessment [ Time Frame: 18 months ]
  Change from the baseline in GAS6 serum levels.
• Anti-drug antibody (ADA) titers [ Time Frame: 18 months ]
  Change from baseline in ADA titer.
• Objective response rate [ Time Frame: 18 months ]
  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 [ Time Frame: 18 months ]
  Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
• Duration of response (DOR) [ Time Frame: 18 months ]
  Measured from the date of partial or complete response to therapy until the cancer progresses.
• Overall survival [ Time Frame: 30 months ]
  Time following the treatment until death.
• CA-125 response rate [ Time Frame: 18 months ]
  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) [ Time Frame: 18 months ]
  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).

Original Secondary Outcome Measures (submitted: August 17, 2018)

• Pharmacokinetics: AUC [ Time Frame: 18 months ]
  Area under the AVB-S6-500 concentration-time curve.
• Pharmacokinetics: Cmax [ Time Frame: 18 months ]
  Maximum observed AVB-S6-500 concentration.
• Pharmacokinetics: Tmax [ Time Frame: 18 months ]
  Time of maximum observed AVB-S6-500 concentration.
• Pharmacokinetics: t1/2 [ Time Frame: 18 months ]
  Apparent terminal half-life of AVB-S6-500.
• Pharmacodynamic marker assessment [ Time Frame: 18 months ]
  Change from the baseline in GAS6 serum levels.
• Anti-drug antibody (ADA) titers [ Time Frame: 18 months ]
  Change from baseline in ADA titer.
• Objective response rate [ Time Frame: 18 months ]
  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 [ Time Frame: 18 months ]
  Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
• Duration of response (DOR) [ Time Frame: 18 months ]
  Measured from the date of partial or complete response to therapy until the cancer progresses.
• Overall survival [ Time Frame: 30 months ]
  Time following the treatment until death.
• CA-125 response rate [ Time Frame: 18 months ]
  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) [ Time Frame: 18 months ]
  Subject QOL will be assessed every 8 weeks during treatment using the FACT-O questionnaire.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Ovarian Cancer

Intervention

• Drug: AVB-S6-500
  AVB-S6-500 is experimental drug
• Drug: Paclitaxel (Pac)
  Paclitaxel is active comparator
  Other Name: Taxol
• Drug: Pegylated liposomal doxorubicin (PLD)
  PLD is active comparator
  Other Name: Doxil
• Other: Placebo
  Placebo comparator

Study Arms

• Experimental: Phase 1b: AVB-S6-500+PLD
  Interventions:

  • Drug: AVB-S6-500
  • Drug: Pegylated liposomal doxorubicin (PLD)
• Experimental: Phase 1b: AVB-S6-500+Pac
  Interventions:

  • Drug: AVB-S6-500
  • Drug: Paclitaxel (Pac)
• Experimental: Phase 2: AVB-S6-500+PLD
  Interventions:

  • Drug: AVB-S6-500
  • Drug: Pegylated liposomal doxorubicin (PLD)
• Experimental: Phase 2: AVB-S6-500+Pac
  Interventions:

  • Drug: AVB-S6-500
  • Drug: Paclitaxel (Pac)
• Active Comparator: Phase 2: Placebo+PLD
  Interventions:

  • Drug: Pegylated liposomal doxorubicin (PLD)
  • Other: Placebo
• Active Comparator: Phase 2: Placebo+Pac
  Interventions:

  • Drug: Paclitaxel (Pac)
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 6, 2020): 53
• Original Estimated Enrollment (submitted: August 17, 2018): 156
• Actual Study Completion Date: December 30, 2022
• Actual Primary Completion Date: January 8, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03639246
• Other Study ID Numbers: AVB500-OC-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Aravive, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Aravive, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Amy Franke; Aravive, Inc.

• PRS Account: Aravive, Inc.
• Verification Date: February 2023