Back to resultsGeldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
Primary Purpose
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Non-Hodgkin Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
tanespimycin
Sponsored by
About this trial
This is an interventional treatment trial for Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Eligibility 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)
Sites / Locations
- University of Nebraska Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (tanespimycin)
Arm Description
Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.
Outcomes
Primary Outcome Measures
Maximum tolerated dose of tanespimycin
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
Changes in the protein expression of the molecular markers will be assessed by western blot analysis.
Pharmacokinetics of tanespimycin
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.
Full Information
NCT ID
NCT00019708
First Posted
July 11, 2001
Last Updated
December 13, 2013
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00019708
Brief Title
Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
Official Title
A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
December 2013
Overall Recruitment Status
Terminated
Study Start Date
June 1999 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment (tanespimycin)
Arm Type
Experimental
Arm Description
Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.
Intervention Type
Drug
Intervention Name(s)
tanespimycin
Other Intervention Name(s)
17-AAG
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum tolerated dose of tanespimycin
Description
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.
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Biomolecular effects of tanespimycin in normal tissues such as peripheral blood and bone marrow mononuclear cells
Description
Changes in the protein expression of the molecular markers will be assessed by western blot analysis.
Time Frame
Up to day 5
Title
Pharmacokinetics of tanespimycin
Description
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.
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean Grem
Organizational Affiliation
University of Nebraska
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
12. IPD Sharing Statement
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Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
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