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

Alternate Title

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Solid Tumors That Cannot Be Removed By Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI MAYO-990102 NCI-T99-0058, NCT00004075, T99-0058

Objectives

1. Determine the maximum tolerated dose and dose-limiting toxicity of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), administered at 2 different dosing schedules, in patients with unresectable solid tumors.
2. Determine the pharmacokinetics of this drug in these patients.
3. Assess the effect of this drug on heat shock protein chaperone complex components and client proteins in lymphoma tissue obtained pre- and post-treatment in patients with relapsed lymphoma.
4. Determine any response to this drug in these patients.

Entry Criteria

Disease Characteristics:

• One of the following diagnoses:
  • Histologically or cytologically confirmed solid tumor*
    • Unresectable disease
  • Hodgkin's or non-Hodgkin's lymphoma
    • Relapsed disease
    • Failed at least 1 prior therapy
    • Neoplastic cells are accessible through biopsy

     [Note: *Only patients with biopsy-accessible superficial tumors or lymphoma are eligible once the maximum tolerated dose has been determined]




• No known standard therapy that is potentially curative or definitely capable of extending life expectancy exists



• No CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:

• More than 4 weeks since prior immunotherapy
• More than 4 weeks since prior biologic therapy
• No concurrent immunotherapy
• No concurrent routine or prophylactic use of a colony-stimulating factor (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy:

• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin or nitrosoureas) and recovered from acute and reversible toxic effects
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent birth control pills
• No concurrent steroids as anti-emetics

Radiotherapy:

• More than 4 weeks since prior radiotherapy
• No prior radiotherapy to more than 25% of the bone marrow
• No prior radiopharmaceuticals
• No concurrent radiotherapy

Surgery:

• Not specified

Other:

• No concurrent 3A4 enzyme inhibitors (e.g., verapamil, erythromycin, miconazole, or ketoconazole)
• No concurrent investigational ancillary therapy
• No concurrent enrollment in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy approaches, or gene therapy) for symptom control or therapeutic intent

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 9 g/dL

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)
• AST no greater than 2.5 times ULN
• Alkaline phosphatase no greater than 2 times ULN (5 times ULN if liver involvement)

Renal:

• Creatinine no greater than 1.25 times ULN

  OR

• Creatinine clearance at least 60 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective nonhormonal contraception
• No uncontrolled infection
• No seizure disorder
• No history of serious allergic reaction to eggs

Expected Enrollment

A total of 58-130 patients (30-72 for group I and 28-58 for group II) will be accrued for this study within 2 years.

Outline

This is a dose-escalation study. Patients are assigned to 1 of 2 treatment groups.

• Group I: Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.



• Group II: Patients receive 17-AAG IV over 1 hour on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 1-6 solid tumor patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, 10 patients with either lymphoma or superficial solid tumors accessible for biopsy are treated as in group II at the MTD.

Patients are followed for 3 months.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Charles Erlichman, MD, Protocol chair		Ph: 507-284-2511 Email: erlichman.charles@mayo.edu
David O. Toft, PhD, Protocol co-chair		Ph: 507-284-2511
Joel M. Reid, PhD, Protocol co-chair		Ph: 507-284-4303
Matthew Ames, PhD, Protocol co-chair		Ph: 507-284-2424
Thomas Witzig, MD, Protocol co-chair		Ph: 507-266-9276 Email: witzig.thomas@mayo.edu

Registry Information
Official Title		A Phase I Trial of 17-Allylaminogeldanamycin (17-AAG) in Solid Tumor and Lymphoma Patients
Trial Start Date		1999-08-16
Registered in ClinicalTrials.gov		NCT00004075
Date Submitted to PDQ		1999-08-26
Information Last Verified		2005-09-08
NCI Grant/Contract Number		P30-CA15083, U01-CA69912

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