Efficacy and Safety Study of AVB-S6-500 in Patients With Platinum-Resistant Recurrent Ovarian Cancer
- Conditions
- Ovarian Cancer
- Interventions
- Registration Number
- NCT03639246
- Lead Sponsor
- Aravive, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 53
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 1b: AVB-S6-500+Pac Paclitaxel (Pac) - Phase 1b: AVB-S6-500+PLD Pegylated liposomal doxorubicin (PLD) - Phase 1b: AVB-S6-500+PLD AVB-S6-500 - Phase 2: Placebo+PLD Placebo - Phase 2: Placebo+Pac Paclitaxel (Pac) - Phase 2: AVB-S6-500+PLD AVB-S6-500 - Phase 2: AVB-S6-500+PLD Pegylated liposomal doxorubicin (PLD) - Phase 2: AVB-S6-500+Pac Paclitaxel (Pac) - Phase 2: Placebo+PLD Pegylated liposomal doxorubicin (PLD) - Phase 2: Placebo+Pac Placebo - Phase 1b: AVB-S6-500+Pac AVB-S6-500 - Phase 2: AVB-S6-500+Pac AVB-S6-500 -
- Primary Outcome Measures
Name Time Method Incidence of Adverse Events (AEs) 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 Pac 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.
Anti-tumor activity of AVB-S6-500 in combination with PLD 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.
- Secondary Outcome Measures
Name Time Method Pharmacokinetics: Tmax 18 months Time of maximum observed AVB-S6-500 concentration.
Duration of response (DOR) 18 months Measured from the date of partial or complete response to therapy until the cancer progresses.
Overall survival 30 months Time following the treatment until death.
Pharmacokinetics: AUC 18 months Area under the AVB-S6-500 concentration-time curve.
Pharmacokinetics: t1/2 18 months Apparent terminal half-life of AVB-S6-500.
Anti-drug antibody (ADA) titers 18 months Change from baseline in ADA titer.
Quality of Life(QOL) 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).
Pharmacokinetics: Cmax 18 months Maximum observed AVB-S6-500 concentration.
Pharmacodynamic marker assessment 18 months Change from the baseline in GAS6 serum levels.
Objective response rate 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 18 months Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
CA-125 response rate 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.
Trial Locations
- Locations (16)
OUHSC-Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Kaiser Permanente Vallejo
🇺🇸Vallejo, California, United States
Kaiser Permanente San Francisco
🇺🇸San Francisco, California, United States
Texas Oncology - Fort Worth
🇺🇸Fort Worth, Texas, United States
Kaiser Permanente Santa Clara
🇺🇸Santa Clara, California, United States
Kaiser Permanente Oakland
🇺🇸Oakland, California, United States
Kaiser Permanente Roseville
🇺🇸Roseville, California, United States
Arizona Oncology
🇺🇸Phoenix, Arizona, United States
Arizona Oncology Associates
🇺🇸Tucson, Arizona, United States
Kaiser Permanente Walnut Creek
🇺🇸Walnut Creek, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Texas Oncology - Austin Central
🇺🇸Austin, Texas, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Texas Oncology - San Antonio Medical Center
🇺🇸San Antonio, Texas, United States