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

Sponsor

Aravive, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03639246

Collaborator

(none)

Enrollment

Locations

Arms

47.8

Anticipated Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: AVB-S6-500 Drug: Paclitaxel (Pac) Drug: Pegylated liposomal doxorubicin (PLD) Other: Placebo	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

53 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 6, 2018

Actual Primary Completion Date :

Jan 8, 2021

Anticipated Study Completion Date :

Dec 1, 2022

Arms and Interventions

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	Drug: Pegylated liposomal doxorubicin (PLD) PLD is active comparator Other Names: Doxil Other: Placebo Placebo comparator
Active Comparator: Phase 2: Placebo+Pac	Drug: Paclitaxel (Pac) Paclitaxel is active comparator Other Names: Taxol Other: Placebo Placebo comparator

Outcome Measures

Primary Outcome Measures

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 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.
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.

Secondary Outcome Measures

Pharmacokinetics: AUC [18 months]
Area under the AVB-S6-500 concentration-time curve.
Pharmacokinetics: Cmax [18 months]
Maximum observed AVB-S6-500 concentration.
Pharmacokinetics: Tmax [18 months]
Time of maximum observed AVB-S6-500 concentration.
Pharmacokinetics: t1/2 [18 months]
Apparent terminal half-life of AVB-S6-500.
Pharmacodynamic marker assessment [18 months]
Change from the baseline in GAS6 serum levels.
Anti-drug antibody (ADA) titers [18 months]
Change from baseline in ADA titer.
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.
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.
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.
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology	Phoenix	Arizona	United States	85016
2	Arizona Oncology Associates	Tucson	Arizona	United States	85711
3	Kaiser Permanente Oakland	Oakland	California	United States	94611
4	Kaiser Permanente Roseville	Roseville	California	United States	95661
5	Kaiser Permanente San Francisco	San Francisco	California	United States	94115
6	Kaiser Permanente Santa Clara	Santa Clara	California	United States	95051
7	Kaiser Permanente Vallejo	Vallejo	California	United States	94589
8	Kaiser Permanente Walnut Creek	Walnut Creek	California	United States	94596
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
10	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
11	Washington University	Saint Louis	Missouri	United States	63110
12	OUHSC-Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
13	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon	United States	97401
14	Texas Oncology - Austin Central	Austin	Texas	United States	78731
15	Texas Oncology - Fort Worth	Fort Worth	Texas	United States	76104
16	Texas Oncology - San Antonio Medical Center	San Antonio	Texas	United States	78240