Clinical Trial: PXD101 and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas

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

Official Title: A Phase 1 Study of PXD101 in Combination With Bortezomib (PS-341) in Patients With Advanced Solid Tumors and Lymphoma

Brief Summary: This phase I trial is studying the side effects and best dose of PXD101 and bortezomib in treating patients with advanced solid tumors or lymphomas. PXD101 and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PXD101 may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving PXD101 together with bortezomib may kill more cancer cells.

Detailed Summary:

OBJECTIVES:

I. Evaluate the safety profile and determine the maximum tolerated dose of PXD101 in combination with bortezomib in patients with advanced solid tumors or lymphomas.

II. Determine the pharmacokinetics of the combination of PXD101 and bortezomib in these patients.

III. Evaluate selected biomarkers of drug effect in these patients. IV. Evaluate the activity of this regimen, in terms of objective response rate, in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1). Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-9 patients receive escalating doses of bortezomib and PXD101 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Blood is collected at baseline and periodically during course 1 of study treatment for pharmacokinetic studies.

After completion of study treatment, patients are followed periodically for 4 weeks.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum tolerated dose of PXD101 in combination with bortezomib [ Time Frame: Day 21 ]
    Defined as the dose level below that which results in drug-related dose limiting toxicity (DLT) in >= 2 of 6 new patients.
  • Frequency and severity of treatment-related adverse events graded per NCI CTCAE version 3.0 [ Time Frame: Day 21 ]
  • Changes in biological markers (p21, cleaved PARP, IkB, p65 Rel A, p-AKT, p-ERK and apoptosis) from pre- to post-treatment [ Time Frame: Baseline and day 21 ]
  • Objective response rate [ Time Frame: 4 weeks ]


Original Primary Outcome:

Current Secondary Outcome: Pharmacokinetics of the combination of PXD101 with bortezomib [ Time Frame: Baseline, end of infusion, then 15 minutes, 30 minutes, 1, 2, 4 and 6 hours from the end of infusion (days 1 and 2) ]

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 5, 2006
Date Started: March 2006
Date Completion:
Last Updated: May 1, 2013
Last Verified: May 2013