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.

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 (Clinical Trial)
• 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: December 6, 2018
• Actual Primary Completion Date: January 8, 2021
• Actual Study Completion Date: December 30, 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 Name: 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 Name: 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 Name: 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 Name: Taxol
Active Comparator: Phase 2: Placebo+PLD	Drug: Pegylated liposomal doxorubicin (PLD); PLD is active comparator; Other Name: Doxil; Other: Placebo; Placebo comparator
Active Comparator: Phase 2: Placebo+Pac	Drug: Paclitaxel (Pac); Paclitaxel is active comparator; Other Name: Taxol; Other: Placebo; Placebo comparator

Outcome Measures

Primary Outcome Measures :

1. Incidence of Adverse Events (AEs) [ Time Frame: 6 months ]
   Measured by the number of patients with AEs in Phase 1 portion of the study.
2. 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.
3. 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.

Secondary Outcome Measures :

1. Pharmacokinetics: AUC [ Time Frame: 18 months ]
   Area under the AVB-S6-500 concentration-time curve.
2. Pharmacokinetics: Cmax [ Time Frame: 18 months ]
   Maximum observed AVB-S6-500 concentration.
3. Pharmacokinetics: Tmax [ Time Frame: 18 months ]
   Time of maximum observed AVB-S6-500 concentration.
4. Pharmacokinetics: t1/2 [ Time Frame: 18 months ]
   Apparent terminal half-life of AVB-S6-500.
5. Pharmacodynamic marker assessment [ Time Frame: 18 months ]
   Change from the baseline in GAS6 serum levels.
6. Anti-drug antibody (ADA) titers [ Time Frame: 18 months ]
   Change from baseline in ADA titer.
7. 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.
8. Disease control rate [ Time Frame: 18 months ]
   Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.
9. Duration of response (DOR) [ Time Frame: 18 months ]
   Measured from the date of partial or complete response to therapy until the cancer progresses.
10. Overall survival [ Time Frame: 30 months ]
    Time following the treatment until death.
11. 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.
12. 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).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology

Phoenix, Arizona, United States, 85016

Arizona Oncology Associates

Tucson, Arizona, United States, 85711

United States, California

Kaiser Permanente Oakland

Oakland, California, United States, 94611

Kaiser Permanente Roseville

Roseville, California, United States, 95661

Kaiser Permanente San Francisco

San Francisco, California, United States, 94115

Kaiser Permanente Santa Clara

Santa Clara, California, United States, 95051

Kaiser Permanente Vallejo

Vallejo, California, United States, 94589

Kaiser Permanente Walnut Creek

Walnut Creek, California, United States, 94596

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02214

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Missouri

Washington University

Saint Louis, Missouri, United States, 63110

United States, Oklahoma

OUHSC-Stephenson Cancer Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Willamette Valley Cancer Institute and Research Center

Eugene, Oregon, United States, 97401

United States, Texas

Texas Oncology - Austin Central

Austin, Texas, United States, 78731

Texas Oncology - Fort Worth

Fort Worth, Texas, United States, 76104

Texas Oncology - San Antonio Medical Center

San Antonio, Texas, United States, 78240

Sponsors and Collaborators

Aravive, Inc.

Investigators

• Study Director: Amy Franke; Aravive, Inc.

More Information

• Responsible Party: Aravive, Inc.
• ClinicalTrials.gov Identifier: NCT03639246
• Other Study ID Numbers: AVB500-OC-002
• First Posted: August 21, 2018
• Last Update Posted: February 13, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Aravive, Inc.:

Ovarian cancer; Platinum resistant

Additional relevant MeSH terms:

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Paclitaxel; Doxorubicin; Liposomal doxorubicin; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors