Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Geldanamycin Analogue in Treating Patients With Advanced Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Completed	18 to 75	Other	CRC-PHASE-I-PH1/074 NCI-T99-0013, EU-99055, NCT00003969, T99-0013

Objectives

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

Entry 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

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)

Patient Characteristics:

Age:

• 18 to 75

Performance status:

• WHO 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• WBC at least 3,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 10.0 g/dL
• Absolute neutrophil count at least 1,500/mm³

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

Expected Enrollment

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

Outcomes

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

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

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.

Banerji U, O'Donnell A, Scurr M, et al.: Phase I pharmacokinetic and pharmacodynamic study of 17-allylamino, 17-demethoxygeldanamycin in patients with advanced malignancies. J Clin Oncol 23 (18): 4152-61, 2005.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer Research UK Clinical Groups at Guy's King's & St. Thomas' Hospitals

Ian Judson, MA, MD, FRCP, Protocol chair		Ph: 44-20-7352-8171

Registry Information
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
Trial Start Date		1998-08-11
Registered in ClinicalTrials.gov		NCT00003969
Date Submitted to PDQ		1999-06-30
Information Last Verified		2000-12-22

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