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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03639246
• Other study ID #: AVB500-OC-002
• Status: Completed
• Phase: Phase 1
• Start date: December 6, 2018
• Est. completion date: December 30, 2022

Study information

• Verified date: February 2023
• Source: Aravive, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 53
• Est. completion date: December 30, 2022
• Est. primary completion date: January 8, 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

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

Other:
• Placebo
Placebo comparator

Locations

Country	Name	City	State
United States	Texas Oncology - Austin Central	Austin	Texas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Texas Oncology - Fort Worth	Fort Worth	Texas
United States	Kaiser Permanente Oakland	Oakland	California
United States	OUHSC-Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Arizona Oncology	Phoenix	Arizona
United States	Kaiser Permanente Roseville	Roseville	California
United States	Washington University	Saint Louis	Missouri
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Kaiser Permanente San Francisco	San Francisco	California
United States	Kaiser Permanente Santa Clara	Santa Clara	California
United States	Arizona Oncology Associates	Tucson	Arizona
United States	Kaiser Permanente Vallejo	Vallejo	California
United States	Kaiser Permanente Walnut Creek	Walnut Creek	California

Sponsors (1)

Lead Sponsor	Collaborator
Aravive, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Adverse Events (AEs)	Measured by the number of patients with AEs in Phase 1 portion of the study.	6 months
Primary	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
Primary	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	Pharmacokinetics: AUC	Area under the AVB-S6-500 concentration-time curve.	18 months
Secondary	Pharmacokinetics: Cmax	Maximum observed AVB-S6-500 concentration.	18 months
Secondary	Pharmacokinetics: Tmax	Time of maximum observed AVB-S6-500 concentration.	18 months
Secondary	Pharmacokinetics: t1/2	Apparent terminal half-life of AVB-S6-500.	18 months
Secondary	Pharmacodynamic marker assessment	Change from the baseline in GAS6 serum levels.	18 months
Secondary	Anti-drug antibody (ADA) titers	Change from baseline in ADA titer.	18 months
Secondary	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
Secondary	Disease control rate	Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.	18 months
Secondary	Duration of response (DOR)	Measured from the date of partial or complete response to therapy until the cancer progresses.	18 months
Secondary	Overall survival	Time following the treatment until death.	30 months
Secondary	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
Secondary	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