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

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies

Brief Summary: This phase I trial is studying the side effects and best dose of giving tanespimycin together with bortezomib in treating patients with advanced solid tumors or lymphomas. (Accrual for lymphoma patients closed as of 11/27/09) Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of tanespimycin by making cancer cells more sensitive to the drug. Combining tanespimycin with bortezomib may kill more cancer cells.

Detailed Summary:

OBJECTIVES:

I. Determine the dose-limiting toxicity and maximum tolerated dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) (tanespimycin) and bortezomib in patients with advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09).

II. Determine changes in biomarkers (e.g., HSP70, client proteins, and ubiquitination of proteins) in peripheral blood mononuclear cells and tumor specimens from patients with advanced solid tumors or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09) treated with this regimen.

III. Determine responses in patients treated with this regimen. IV. Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive tanespimycin intravenously (IV) over 1-2 hours and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of tanespimycin and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 12 additional patients are treated as above* at the MTD.

NOTE: *Bortezomib is not administered on day 1 of course 1 only. Patients are followed at 3 months.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors [ Time Frame: At 3 weeks ]
    Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of the solid tumor patients (at least 2 of a maximum of 6 new patients).
  • Toxicity of tanespimycin in combination with bortezomib in the treatment of solid tumors [ Time Frame: At 3 weeks ]
    Defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal common toxicity criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading.
  • Changes in biomarkers in peripheral blood mononuclear cells and tumor specimens from patients with advanced solid tumors or lymphomas [ Time Frame: Baseline, days 4, 8, and 11 of course 1, and at the end of treatment study ]
    Changes in the levels of expressions of HSP70, client proteins, and ubquitination of proteins in PBMC at the different dose levels as well as at the different time points will be descriptively summarized. The degree of proteasome inhibition will be quantitated whenever possible and the results will be displayed graphically and analyzed using simple descriptive statistics.
  • Responses in patients treated with this

    Original Primary Outcome:

    Current Secondary Outcome:

    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: November 9, 2004
    Date Started: November 2004
    Date Completion:
    Last Updated: February 21, 2014
    Last Verified: October 2011