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
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: 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 September 16, 2014