VTX-2337 and Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer
RATIONALE: Biological therapies, such as VTX-2337, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving VTX-2337 together with liposomal doxorubicin hydrochloride may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of VTX-2337 and liposomal doxorubicin hydrochloride in treating patients with recurrent or persistent ovarian epithelial, fallopian tube, or peritoneal cavity cancer.
Fallopian Tube Cancer
Primary Peritoneal Cavity Cancer
Drug: TLR8 agonist VTX-2337
Drug: pegylated liposomal doxorubicin hydrochloride
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of VTX-2337 (IND #78,416) in Combination With Doxil® (NSC# 712227) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer|
- First-cycle dose-limiting toxicities [ Designated as safety issue: Yes ]
- Frequency and severity of toxicities as assessed by CTCAE [ Designated as safety issue: Yes ]
- Immune activation (e.g., Th1, cytokines) [ Designated as safety issue: No ]
- Pharmacokinetic measures of TLR8 agonist VTX-2337 [ Designated as safety issue: No ]
- Pharmacokinetic measures of pegylated liposomal doxorubicin hydrochloride [ Designated as safety issue: No ]
|Study Start Date:||April 2011|
|Estimated Primary Completion Date:||February 2014 (Final data collection date for primary outcome measure)|
- To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of VTX-2337 when administered in combination with pegylated liposomal doxorubicin (Doxil®) 40 mg/m^2 and the associated DLTs based on adverse events that occur in cycle 1 for this combination in women with recurrent or persistent, epithelial ovarian, fallopian tube, or primary peritoneal cancer.
- To examine the tolerability of the combination at the MTD of VTX-2337 (assessed in combination with Doxil 40 mg/m^2) with Doxil 50 mg/m^2.
- To determine recommended phase II dose (RP2D) of VTX-2337 in combination with Doxil.
- To assess the biological effects (immune activation) of VTX-2337 in combination with Doxil. (Translational research)
- To assess the pharmacokinetics of Doxil and VTX-2337 in patients receiving VTX-2337 in combination with Doxil. (Translational research)
- To assess the anti-tumor activity of VTX-2337 when administered concomitantly with Doxil in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer. (Exploratory)
- To assess the effect of TLR8 polymorphisms on the biological (immune) and clinical effects of VTX-2337 in combination with Doxil. (Exploratory)
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive TLR8 agonist VTX-2337 subcutaneously on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically during courses 1 and 2 for pharmacokinetic, pharmacogenomic, and other research studies.
After completion of study treatment, patients are followed up every 3 months for 1 year.
|United States, Arizona|
|Gynecologic Oncology Group of Arizona|
|Phoenix, Arizona, United States, 85012|
|Saint Joseph's Hospital and Medical Center|
|Phoenix, Arizona, United States, 85013|
|United States, Colorado|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion|
|Aurora, Colorado, United States, 80045|
|United States, Iowa|
|University of Iowa Hospitals and Clinics|
|Iowa City, Iowa, United States, 52242|
|United States, Kentucky|
|University of Kentucky|
|Lexington, Kentucky, United States, 40536|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Ohio|
|MetroHealth Medical Center|
|Cleveland, Ohio, United States, 44109|
|United States, Oklahoma|
|University of Oklahoma Health Sciences Center|
|Oklahoma City, Oklahoma, United States, 73104|
|United States, Pennsylvania|
|Fox Chase Cancer Center|
|Philadelphia, Pennsylvania, United States, 19111-2497|
|United States, Rhode Island|
|Women and Infants Hospital|
|Providence, Rhode Island, United States, 02905|
|Principal Investigator:||Bradley J. Monk, MD||Chao Family Comprehensive Cancer Center|