A Phase I Study Of 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17DMAG) With Evaluation Of Hsp90 Client Proteins In Subjects With Solid Tumors And Lymphomas

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically confirmed malignant solid tumor OR lymphoma

- Metastatic or unresectable disease

- Standard curative or palliative measures are not available OR are associated with
minimal survival benefit

- No known brain metastases

- Treated brain metastases allowed provided they have been stable ≥ 6 months
without steroids or anti-seizure medications

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy

- More than 3 months

Hematopoietic

- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3

- Hemoglobin > 8 g/dL

Hepatic

- AST and ALT ≤ 2 times upper limit of normal

- Bilirubin ≤ 1.5 times normal

- PT and PTT ≤ 1.5 times normal (unless due to the presence of lupus anticoagulant or
stable anticoagulation)

Renal

- Creatinine normal OR

- Creatinine clearance ≥ 60 mL/min

Cardiovascular

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No orthostatic hypotension > grade 2 (requiring more than brief fluid replacement or
other therapy OR with physiological consequences)

- No New York Heart Association class III or IV heart failure

- LVEF ≥ 40% by MUGA

- QTc ≤ 450 msec (470 msec for women)

- No congenital long QT syndrome

- No myocardial infarction within the past year

- No active ischemic heart disease within the past year

- No history of uncontrolled dysrhythmias

- No history of serious ventricular arrhythmia (ventricular fibrillation or ventricular
tachycardia > 3 premature ventricular contractions in a row)

- Not requiring antiarrhythmic drugs

- No poorly controlled angina

- No left bundle branch block

Pulmonary

- No uncontrolled symptomatic pulmonary disease, including any of the following:

- Dyspnea off or on exertion

- Paroxysmal nocturnal dyspnea

- Severe chronic obstructive/restrictive pulmonary disease requiring daily chronic
medications and oxygen

- Must not meet the Medicare criteria for home oxygen

- No sufficiently compromised pulmonary status as measured by baseline pulmonary
function tests and DLCO

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 2 months after study
participation

- No known HIV positivity

- No hyponatremia indicated by sodium < 130 mmol/L

- No known immunodeficiency syndromes

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to 17-dimethylaminoethylamino-17-demethoxygeldanamycin
(geldanamycin or 17-AAG)

- No concurrent uncontrolled illness

- No active or ongoing uncontrolled infection

- No psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 4 weeks since prior biologic therapy and recovered

- No concurrent prophylactic growth factors

Chemotherapy

- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin, 8
weeks for UCN-01) and recovered

Endocrine therapy

- See Disease Characteristics

- Concurrent hormonal therapy for prostate cancer allowed provided patient has
metastatic disease that has progressed despite prior hormonal therapy

Radiotherapy

- More than 4 weeks since prior radiotherapy and recovered

- No prior radiotherapy that included the heart in the field (e.g., mantle
radiotherapy)

Surgery

- At least 4 weeks since prior major surgery

Other

- At least 2 weeks since prior participation in a phase 0 study

- Concurrent bisphosphonates for any cancer allowed

- Concurrent preventative doses of aspirin or non-steroidal anti-inflammatory drugs
allowed

- No concurrent drugs that may prolong QTc interval

- No concurrent full anticoagulation on a regular basis

- No concurrent prophylactic antiemetics

- No other concurrent investigational agents or therapies

- No other concurrent anticancer agents or therapies