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

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00004075

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

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 17-N-allylamino-17-demethoxygeldanamycin in treating patients with solid tumors that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: tanespimycin	Phase 1

Detailed Description

OBJECTIVES:

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.
Determine the pharmacokinetics of this drug in these patients.
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.
Determine any response to this drug in these patients.

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.

PROJECTED ACCRUAL: 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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Phase I Trial of 17-Allylaminogeldanamycin (17-AAG) in Solid Tumor and Lymphoma Patients

Study Start Date :

Aug 1, 1999

Actual Primary Completion Date :

Jan 1, 2007

Actual Study Completion Date :

Jan 1, 2007

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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/mm^3
Platelet count at least 100,000/mm^3
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

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