Geldanamycin Analogue in Treating Patients With Advanced Cancer
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
OBJECTIVES:
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Determine the maximum tolerated dose for a geldanamycin analogue, 17-allylamino-17-demethoxygeldanamycin (AAG), in patients with advanced malignancies.
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Determine the toxic effects and dose-limiting toxicity of AAG in this patient population.
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Determine the safe dose of AAG for a Phase II study.
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Measure the pharmacokinetic and pharmacodynamic profiles of AAG in these patients.
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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 Design
Outcome Measures
Primary Outcome Measures
- Recommended phase II dose of 17-allylamino-17-demethoxygeldanamycin (17-AAG) at 4 weeks []
Secondary Outcome Measures
- 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 []
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
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Histologically or cytologically proven malignancies refractory to conventional treatment or for which no standard therapy exists
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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:
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WBC at least 3,500/mm^3
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Platelet count at least 100,000/mm^3
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Hemoglobin at least 10.0 g/dL
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Absolute neutrophil count at least 1,500/mm^3
Hepatic:
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Bilirubin less than 1.0 mg/dL
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AST and ALT no greater than 2.5 times upper limit of normal if due to liver metastases
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No chronic liver disease
Renal:
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Creatinine less than 1.47 mg/dL OR
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Creatinine clearance greater than 60 mL/min
Cardiovascular:
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No myocardial infarction within the past 6 months
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No angina requiring treatment within the past 6 months
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No uncompensated coronary artery disease by electrocardiogram or physical examination
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No prior transient ischemic attacks, stroke, or peripheral vascular disease
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LVEF at least 45%
Other:
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Not pregnant or nursing
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Negative pregnancy test
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Fertile patients must use effective contraception during and for 4 weeks after study
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No allergy to egg products
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No nonmalignant systemic disease that would increase risk
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No active uncontrolled infection
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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:
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At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas and mitomycin) and recovered
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No other concurrent chemotherapy
Endocrine therapy:
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At least 4 weeks since other prior endocrine therapy and recovered
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Concurrent corticosteroids for symptom control allowed if no change in dose requirement within 2 weeks prior to study
Radiotherapy:
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At least 4 weeks since prior radiotherapy (except for palliative reasons) and recovered
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Concurrent radiotherapy allowed for control of bone pain or as indicated
Surgery:
- Not specified
Other:
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No other concurrent investigational treatment
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No concurrent treatment with drugs interfering with hepatic CYP3A4 metabolism (e.g., grapefruit juice or warfarin)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRC-PHASE-I-PH1/074
- CDR0000067170
- NCI-T99-0013
- EU-99055