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

December 13, 2013 updated by: National Cancer Institute (NCI)

A Phase I and Pharmacologic Study of 17-(Allylamino)-17-Demethoxygeldanamycin (AAG, NSC 330507) in Adult Patients With Solid Tumors

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

45

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (tanespimycin)
Patients will receive infusions of tanespimycin analogue twice a week in weeks 1 and 3.
Drug: tanespimycin
Given IV
Other Names:
  • 17-AAG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum tolerated dose of tanespimycin
Time Frame: 28 days
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.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomolecular effects of tanespimycin in normal tissues such as peripheral blood and bone marrow mononuclear cells
Time Frame: Up to day 5
Changes in the protein expression of the molecular markers will be assessed by western blot analysis.
Up to day 5
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
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.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Jean Grem, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 1999

Primary Completion (Actual)

April 1, 2010

Study Registration Dates

First Submitted

July 11, 2001

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

December 16, 2013

Last Update Submitted That Met QC Criteria

December 13, 2013

Last Verified

December 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00819 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • UNMC 170-04 (Other Identifier: University of Nebraska Medical Center)
  • CDR0000066965
  • T98-0075 (Other Identifier: CTEP)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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