Geldanamycin Analogue in Treating Patients With Advanced Cancer

June 25, 2013 updated by: Cancer Research UK

A Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) (NSC 330507) Via Intravenous Administration in Patients With Advanced Malignancies

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: This phase I trial is studying the side effects and best dose of a geldanamycin analogue in treating patients with advanced cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose for a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies.
  • Determine the toxic effects and dose-limiting toxicity of AAG in this patient population.
  • Determine the safe dose of AAG for a Phase II study.
  • Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients.
  • Assess time to tumor progression and any antitumor activity in patients treated with AAG.

OUTLINE: This is a dose-escalation study.

Patients receive a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), IV over 15-30 minutes every week. Treatment continues 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 at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 4 weeks.

PROJECTED ACCRUAL: Approximately 20-40 patients will be accrued for this study.

Study Type

Interventional

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 Kingdom
    • England
      • London, England, United Kingdom, SW3 6JJ
        • Royal Marsden NHS Foundation Trust - London

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

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven malignancies refractory to conventional treatment or for which no standard therapy exists
  • Primary brain tumor or brain metastases allowed if stable symptoms within 2 weeks prior to study and able to give informed consent

PATIENT CHARACTERISTICS:

Age:

  • 18 to 75

Performance status:

  • WHO 0-2

Life expectancy:

  • At least 3 months

Hematopoietic:

  • WBC at least 3,500/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 10.0 g/dL
  • Absolute neutrophil count at least 1,500/mm^3

Hepatic:

  • Bilirubin less than 1.0 mg/dL
  • AST and ALT no greater than 2.5 times upper limit of normal if due to liver metastases
  • No chronic liver disease

Renal:

  • Creatinine less than 1.47 mg/dL OR
  • Creatinine clearance greater than 60 mL/min

Cardiovascular:

  • No myocardial infarction within the past 6 months
  • No angina requiring treatment within the past 6 months
  • No uncompensated coronary artery disease by electrocardiogram or physical examination
  • No prior transient ischemic attacks, stroke, or peripheral vascular disease
  • LVEF at least 45%

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 weeks after study
  • No allergy to egg products
  • No nonmalignant systemic disease that would increase risk
  • No active uncontrolled infection
  • No diabetes mellitus with evidence of severe peripheral vascular disease or diabetic ulcers

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
  • No other concurrent chemotherapy

Endocrine therapy:

  • At least 4 weeks since other prior endocrine therapy and recovered
  • Concurrent corticosteroids for symptom control allowed if no change in dose requirement within 2 weeks prior to study

Radiotherapy:

  • At least 4 weeks since prior radiotherapy (except for palliative reasons) and recovered
  • Concurrent radiotherapy allowed for control of bone pain or as indicated

Surgery:

  • Not specified

Other:

  • No other concurrent investigational treatment
  • No concurrent treatment with drugs interfering with hepatic CYP3A4 metabolism (e.g., grapefruit juice or warfarin)

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Recommended phase II dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) at 4 weeks

Secondary Outcome Measures

Outcome Measure
Heat shock protein 90 (HSP90) client protein and co-chaperone changes during first course of treatment
Pharmacokinetic profile of 17-AAG during the first course of treatment

Collaborators and Investigators

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

Sponsor

Cancer Research UK

Investigators

  • Study Chair: Ian R. Judson, MA, MD, FRCP, Royal Marsden NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

August 1, 1998

Study Completion (ACTUAL)

January 1, 2007

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

June 26, 2013

Last Update Submitted That Met QC Criteria

June 25, 2013

Last Verified

December 1, 2000

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • CRC-PHASE-I-PH1/074
  • CDR0000067170 (REGISTRY: PDQ (Physician Data Query))
  • NCI-T99-0013
  • EU-99055

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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