The purpose of this study is to compare the overall survival of patients treated with VTX-2337 + pegylated liposomal doxorubicin (PLD) versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer. VTX-2337, a small molecule agonist of Toll-like Receptor 8 (TLR8), activates multiple components of the innate immune system and is being developed as a novel therapeutic agent for use in oncology. Experimental data obtained in an animal model of ovarian cancer supports the combination of VTX-2337 with PLD. In this model, the combination of VTX-2337 and PLD resulted in a significant reduction in tumor growth compared to either agent alone and an increase in the number of T lymphocytes infiltrating the tumor. The combination of PLD and VTX-2337 has been tested in a small number of women with ovarian cancer in a Phase 1b study and appears to be generally well-tolerated.
OBJECTIVES Primary Objectives: * To compare the overall survival (OS) of patients treated with VTX-2337 + PLD versus those treated with PLD alone in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer. * To compare the progression-free survival (PFS) between the two treatment groups using Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST). Secondary Objectives: * To compare the progression-free survival (PFS) between the two treatment groups using Response Evaluation Criteria In Solid Tumors (RECIST 1.1). * To compare the nature, frequency and severity of drug-related adverse events (AEs) between the two treatment groups. Exploratory Objectives: * To compare the best overall response rate (ORR) and duration of response (based on the probability of being in response function \[PBRF\]) between the two treatment groups using irRECIST and RECIST 1.1. * To compare the disease control rate (DCR) between the two treatment groups using irRECIST and RECIST 1.1. * To assess the impact of immune status and response on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. * To assess the effect of TLR8 polymorphisms and BRCA1/BRCA2 mutations on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. * To assess the effect of immune cell subsets, as measured by immunohistochemistry and micro RNA in primary tumor tissue (e.g. immune score), on the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. * To assess whether the presence of autoantibodies to tumor-derived proteins are predictive of the clinical effects (OS, PFS, DCR, ORR, PBRF, AEs) of study treatment. OUTLINE: This is Phase 2 multicenter clinical study to evaluate the efficacy and safety of the combination of VTX-2337 + PLD compared to PLD + Placebo. The dosing schedule will be the same for both treatment arms, and will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 or placebo on Day 3, Day 10, and Day 17 for the first 4 cycles. Starting with cycle 5, the dose regimen will be PLD on Day 1 plus VTX-2337 or placebo on Day 3. Blood samples are collected periodically during cycle 1 for pharmacodynamics, pharmacogenomics, and other research studies. Patients will receive therapy until disease progression based on Immune-Related RECIST or until adverse effects prohibit further therapy. Following treatment completion, all patients will be followed with physical exams and histories every three months for the first two years, and then every six months for the next three years, and then
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
297
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Winthrop P. Rockefeller Cancer Institute - University of Arkansas
Little Rock, Arkansas, United States
Providence Saint Joseph Medical Center
Burbank, California, United States
Kaiser Permanente Medical Center
Hayward, California, United States
Long Beach Memorial Medical Center
Long Beach, California, United States
Overall Survival
Comparison of duration of survival between the 2 treatment groups
Time frame: Survival is measured from date of enrollment and randomization on the study until death from any cause, or if alive at last contact, date of last contact.
Progression-free Survival (PFS)
Comparison of PFS between the 2 treatment groups
Time frame: Progression-free survival is measured from enrollment and randomization on the study until first indication of progression based on irRECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment.
Frequency and Severity of Adverse Events (AEs)
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE can be unfavorable and unintended sign, symptom, or disease which is temporally associated with the use of investigational product (IP), whether or not considered related to the IP. A serious AE = an AE occurring at any dose that: • Results in death • Is life- threatening • Requires or prolongs existing inpatient hospitalization • Results in persistent or significant disability/incapacity • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to IP and graded the severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0: Grade (GR) 1 = Mild; asymptomatic or mild symptoms; GR 2 = Moderate (minimal, local or noninvasive intervention indicated); GR 3 = Severe or medically significant; GR 4 = Life-threatening; GR 5 = Death
Time frame: Assessed during each cycle of therapy and within 30 days after the last cycle of therapy
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Kaiser Permanente Medical Center
Oakland, California, United States
Kaiser Permanente Medical Center
Roseville, California, United States
Sutter Cancer Center
Sacramento, California, United States
Kaiser Permanente Medical Center
Sacramento, California, United States
Kaiser Permanente Medical Center
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