Clinical trial NCT01666444
Conditions: Epithelial Ovarian Cancer Fallopian Tube Cancer Primary Peritoneal Cancer
Keywords: recurrent epithelial ovarian cancer recurrent fallopian tube cancer recurrent primary peritoneal cavity cancer ovarian serous cystadenocarcinoma ovarian endometrioid adenocarcinoma ovarian mucinous cystadenocarcinoma ovarian undifferentiated adenocarcinoma ovarian clear cell cystadenocarcinoma ovarian mixed epithelial carcinoma Brenner tumor
Sponsor: Celgene
Start date: 2012-10-31; Completion date: 2016-07-31
Enrollment: 297 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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

Arms: arm 1: The dosing schedule will be be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus VTX-2337 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 on Day 3 only, without additional doses of VTX-2337 on Days 10 and Day 17. arm 2: The dosing schedule will be based on a 28-day cycle. The starting dose schedule is PLD on Day 1 plus 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 placebo on Day 3 only.
Interventions: intervention 1: pegylated liposomal doxorubicin (PLD) intervention 2: VTX-2337 intervention 3: Placebo
Intervention descriptions: intervention 1: None intervention 2: TLR8 Agonist intervention 3: None

Protocol documents: