Geldanamycin Analogue in Treating Patients With Advanced Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003969
First received: November 1, 1999
Last updated: June 25, 2013
Last verified: December 2000
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: tanespimycin
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Pharmacokinetic and Pharmacodynamic Study of 17-Allylamino-17-Demethoxygeldanamycin (17-AAG) (NSC 330507) Via Intravenous Administration in Patients With Advanced Malignancies

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Recommended phase II dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) at 4 weeks [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Heat shock protein 90 (HSP90) client protein and co-chaperone changes during first course of treatment [ Designated as safety issue: No ]
  • Pharmacokinetic profile of 17-AAG during the first course of treatment [ Designated as safety issue: No ]

Study Start Date: August 1998
Study Completion Date: January 2007
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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003969

Locations
United Kingdom
Royal Marsden NHS Foundation Trust - London
London, England, United Kingdom, SW3 6JJ
Sponsors and Collaborators
Cancer Research UK
Investigators
Study Chair: Ian R. Judson, MA, MD, FRCP Royal Marsden NHS Foundation Trust
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00003969     History of Changes
Other Study ID Numbers: CRC-PHASE-I-PH1/074, CDR0000067170, NCI-T99-0013, EU-99055
Study First Received: November 1, 1999
Last Updated: June 25, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

ClinicalTrials.gov processed this record on April 17, 2014