Clinical trial NCT03639246: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Keywords: Ovarian cancer
Platinum resistant
Lead sponsor: Aravive, Inc.
Sponsor class: INDUSTRY
First posted: 2018-08-21
Enrollment: 53
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of Adverse Events (AEs)
timeFrame: 6 months
measure: Anti-tumor activity of AVB-S6-500 in combination with PLD
timeFrame: 18 months
measure: Anti-tumor activity of AVB-S6-500 in combination with Pac
timeFrame: 18 months
Secondary outcomes:
measure: Pharmacokinetics: AUC
timeFrame: 18 months
measure: Pharmacokinetics: Cmax
timeFrame: 18 months
measure: Pharmacokinetics: Tmax
timeFrame: 18 months
measure: Pharmacokinetics: t1/2
timeFrame: 18 months
measure: Pharmacodynamic marker assessment
timeFrame: 18 months
measure: Anti-drug antibody (ADA) titers
timeFrame: 18 months
measure: Objective response rate
timeFrame: 18 months
measure: Disease control rate
timeFrame: 18 months
measure: Duration of response (DOR)
timeFrame: 18 months
measure: Overall survival
timeFrame: 30 months
measure: CA-125 response rate
timeFrame: 18 months
measure: Quality of Life(QOL)
timeFrame: 18 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Arizona Oncology
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Oakland
country: United States
facility: Kaiser Permanente Oakland
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Roseville
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Santa Clara
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Vallejo
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Walnut Creek
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Oklahoma City
country: United States
facility: OUHSC-Stephenson Cancer Center
state: Oklahoma
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Austin
country: United States
facility: Texas Oncology - Austin Central
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center
state: Texas
Study officials:
affiliation: Aravive, Inc.
name: Amy Franke
role: STUDY_DIRECTOR
References: