Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00019708
First received: July 11, 2001
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

Phase I trial to study the effectiveness of geldanamycin analogue in treating patients who have advanced solid tumors or non-Hodgkin's lymphoma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die.


Condition Intervention Phase
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Nodal Marginal Zone B-cell Lymphoma
Non-Hodgkin Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Small Lymphocytic Lymphoma
Splenic Marginal Zone Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Small Lymphocytic Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: tanespimycin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose of tanespimycin [ Time Frame: 28 days ] [ Designated as safety issue: No ]
    DLT are defined as any greater than or equal to grade 3 non-hematologic toxicity (except for alopecia of any grade, grade 3 nausea or vomiting during less than maximal antiemetic therapy, and grade 3 fever in the absence of neutropenia and infection), any grade 4 hematologic toxicity (except for anemia of any grade), or the inability to resume treatment by day 42 (longer than two week delay) because of drug related toxicity.


Secondary Outcome Measures:
  • Biomolecular effects of tanespimycin in normal tissues such as peripheral blood and bone marrow mononuclear cells [ Time Frame: Up to day 5 ] [ Designated as safety issue: No ]
    Changes in the protein expression of the molecular markers will be assessed by western blot analysis.

  • Pharmacokinetics of tanespimycin [ Time Frame: Pre-infusion, 20 minutes, 40, 50, 60 (end of infusion), 70, 80, 95 and 110 minutes, and 2.5, 3, 4, 5, 6.5, 8, 10, 14 and 24 hours ] [ Designated as safety issue: No ]
    Determined by HPLC with photodiode array detection. The pharmacokinetic parameters that will be determined for parent drug include the maximum plasma concentration (Cmax), time of maximum plasma concentration (Tmax), area under the concentration-time curve (AUC), terminal half-life, clearance and volume of distribution.


Enrollment: 45
Study Start Date: June 1999
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (tanespimycin)
Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.
Drug: tanespimycin
Given IV
Other Name: 17-AAG

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose of geldanamycin analogue (AAG) in patients with advanced solid tumors.

II. To determine the toxic effects of this drug in this patient population. III. To determine the biochemical and molecular effects of this drug in normal and accessible tumor tissue in these patients.

IV. To determine the pharmacokinetics of this drug in these patients. V. To assess any antitumor activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive geldanamycin analogue (AAG) IV over 1-6 hours once daily on days 1, 4, 15, and 18. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of AAG 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. Once the MTD is determined, an additional 10 patients are treated at the MTD.

Patients are followed every 6 weeks.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Criteria:

  • Platelet count at least 100,000/mm^3
  • No leukemia
  • No active CNS involvement with tumor
  • ECOG 0-2
  • Life expectancy: at least 3 months
  • Absolute neutrophil count at least 2,000/mm^3
  • No New York Heart Association class III or IV heart failure
  • No history of myocardial infarction within the past year
  • Bilirubin =< upper limit of normal (ULN)
  • AST no greater than 2 times ULN (no greater than 98 U/L)
  • No uncontrolled dysrhythmias
  • No poorly controlled angina
  • No serious ventricular arrhythmia (i.e., ventricular tachycardia (VT) or ventricular fibrillation (VF) >= 3 beats in a row)
  • QTc interval =< 450 msec for men or =< 470 msec for women
  • LVEF >= 40% by MUGA
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • HIV negative
  • No other serious medical condition that would preclude study participation
  • No serious hypersensitivity to egg products
  • No concurrent anticancer immunotherapy
  • At least 4 weeks since prior chemotherapy and recovered
  • No other concurrent anticancer chemotherapy (e.g., cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] or mechlorethamine, vincristine, procarbazine, and prednisone [MOPP])
  • No concurrent anticancer hormonal therapy
  • Concurrent glucocorticoids as antiemetics for nonmalignant disease allowed
  • At least 4 weeks since prior radiotherapy and recovered
  • No concurrent radiotherapy
  • No concurrent major surgery
  • No concurrent anticancer glucocorticoids
  • Creatinine =< ULN or Creatinine clearance at least 60 mL/min
  • No concurrent medications that cause QTc prolongation
  • Histologically confirmed advanced solid tumor for which no curative therapy exists
  • Non-Hodgkin's lymphoma allowed
  • No concurrent drugs that interfere with hepatic CYP3A4 metabolism (e.g., grapefruit juice, ketoconazole, fluconazole, itraconazole, cyclosporine, erythromycin, clarithromycin, cimetidine, terfenadine, astemizole, indinavir, or nelfinavir mesylate)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019708

Locations
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
Sponsors and Collaborators
Investigators
Principal Investigator: Jean Grem University of Nebraska
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00019708     History of Changes
Obsolete Identifiers: NCT00001804
Other Study ID Numbers: NCI-2009-00819, NCI-2009-00819, UNMC 170-04, CDR0000066965, UNMC 170-04, T98-0075
Study First Received: July 11, 2001
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, B-Cell, Marginal Zone
Neoplasms
Lymphoma, Mantle-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Leukemia, Lymphoid
Leukemia

ClinicalTrials.gov processed this record on July 29, 2014