TLR8 Agonist VTX-2337 and Pegylated Liposomal Doxorubicin Hydrochloride or Paclitaxel in Treating Patients With Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Peritoneal Cavity Cancer
|ClinicalTrials.gov Identifier: NCT01294293|
Recruitment Status : Completed
First Posted : February 11, 2011
Last Update Posted : December 25, 2014
|Condition or disease||Intervention/treatment||Phase|
|Malignant Ovarian Mixed Epithelial Tumor Ovarian Brenner Tumor Ovarian Clear Cell Cystadenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Mucinous Cystadenocarcinoma Ovarian Serous Cystadenocarcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Undifferentiated Ovarian Carcinoma||Drug: TLR8 Agonist VTX-2337 Other: Diagnostic Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Pegylated Liposomal Doxorubicin Hydrochloride Drug: Paclitaxel||Phase 1|
I. To determine the maximum tolerated doses (MTD) and dose limiting toxicities (DLTs) of VTX-2337 when administered in combination with pegylated liposomal doxorubicin (PLD; Doxil, Lipodox™) 40 mg/m2 in Regimen 1 and when administered in combination with weekly paclitaxel 80 mg/m2 in Regimen 2, and the associated DLTs based on adverse events that occur in cycle 1 for each of these combinations in women with recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer.
II. To examine the tolerability of the combination at the MTD of VTX-2337 assessed in combination with PLD 40 mg/m2 and with PLD 50 mg/m2 in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
III. To determine recommended phase II doses (RP2D) of VTX-2337 in combination with PLD in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
I. To assess the biological effects (immune activation) of VTX-2337 in combination with PLD in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
II. To assess the pharmacokinetics in patients receiving VTX-2337 in combination with PLD in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
III. To assess the tolerability (including CTCAE v4 Grade 3/4 allergic reaction) of weekly paclitaxel 80 mg/m2 when administered without corticosteroid premedication (Regimen 2 only).
I. To assess the anti-tumor activity of VTX-2337 when administered concomitantly with PLD in Regimen 1 and when administered concomitantly with weekly paclitaxel in Regimen 2 in patients with recurrent or persistent epithelial ovarian fallopian tube or primary peritoneal cancer.
II. To assess the effect of TLR8 polymorphisms on the biological (immune) and clinical effects of VTX-2337 in combination with PLD in Regimen 1 and in combination with weekly paclitaxel in Regimen 2.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive TLR8 agonist VTX-2337 subcutaneously (SC) on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 subcutaneously on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of VTX-2337 in Combination With Pegylated Liposomal Doxorubicin (PLD; NSC# 712227) or in Combination With Weekly Pactilaxel (NSC #673089) in Patients With Recurrent or Persistent Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer|
|Study Start Date :||March 2011|
|Primary Completion Date :||July 2014|
Experimental: Treatment (TLR8 agonist VTX-2337, PLD, and Paclitaxel)
Patients receive TLR8 agonist VTX-2337 SC on days 3, 10, and 17 and pegylated liposomal doxorubicin hydrochloride IV over 60 minutes on day 1 or TLR8 agonist VTX-2337 SC on days 1, 8, and 15 and paclitaxel IV over 60 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: TLR8 Agonist VTX-2337
Other Names:Other: Diagnostic Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
Other Name: pharmacological studiesDrug: Pegylated Liposomal Doxorubicin Hydrochloride
Other Names:Drug: Paclitaxel
- First-cycle dose-limiting toxicities [ Time Frame: 28 days ]
- Frequency and severity of toxicities as assessed by CTCAE [ Time Frame: Up to 1 year ]
- Immune activation (e.g., Th1, cytokines) [ Time Frame: Up to 1 year ]Immune response endpoints (e.g., Th1 cytokines) will be summarized with simple descriptive statistics and analyzed with linear mixed models accounting for the longitudinal aspect of the data.
- Pharmacokinetic measures of TLR8 agonist VTX-2337 [ Time Frame: Baseline, 0.5, 2, 4, 8, and 24 hours after TLR8 agonist VTX-2337 injection ]
- Pharmacokinetic measures of pegylated liposomal doxorubicin hydrochloride [ Time Frame: Baseline, 0.5, 2, 4, 8, and 24 hours after TLR8 agonist VTX-2337 injection ]
- Pharmacokinetic measures of paclitaxel [ Time Frame: Baseline, 0.5, 2, 4, 8, and 24 hours after TLR8 agonist VTX-2337 injection ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01294293
|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/Markey Cancer Center|
|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|
|United States, Rhode Island|
|Women and Infants Hospital|
|Providence, Rhode Island, United States, 02905|
|Principal Investigator:||Bradley Monk||NRG Oncology|