Clinical Trial: 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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Epith

Brief Summary: This phase I trial is studying the side effects and best dose of TLR8 agonist VTX-2337 and pegylated liposomal doxorubicin hydrochloride in treating patients with recurrent or persistent ovarian epithelial, fallopian tube, or peritoneal cavity cancer. Biological therapies, such as TLR8 agonist VTX-2337, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving TLR8 agonist VTX-2337 together with pegylated liposomal doxorubicin hydrochloride or paclitaxel may kill more tumor cells.

Detailed Summary:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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).

TERTIARY OBJECTIVES:

I. To assess the anti-tumor activity of VTX-2337 when administered
Sponsor: Gynecologic Oncology Group

Current Primary Outcome:

  • First-cycle dose-limiting toxicities [ Time Frame: 28 days ]
  • Frequency and severity of toxicities as assessed by CTCAE [ Time Frame: Up to 1 year ]


Original Primary Outcome:

  • First-cycle dose-limiting toxicities
  • Frequency and severity of toxicities as assessed by CTCAE


Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • Immune activation (e.g., Th1, cytokines)
  • Pharmacokinetic measures of TLR8 agonist VTX-2337
  • Pharmacokinetic measures of pegylated liposomal doxorubicin hydrochloride


Information By: Gynecologic Oncology Group

Dates:
Date Received: February 10, 2011
Date Started: March 2011
Date Completion:
Last Updated: December 23, 2014
Last Verified: December 2014