An Open-Labeled Non-Randomized Phase I Study of 17-N-allylamino-17-demethoxy Geldanamycin (17AAG) Administered With Irinotecan (CPT-11) in Patients With Advanced Solid Tumors

Inclusion Criteria:

- Histologically confirmed solid tumor, excluding primary CNS tumors

- Locally advanced or metastatic disease that is refractory to standard therapy OR
for which no standard therapy exists

- Tumor assessible for biopsy by Tru-cut^®, CT guidance, or endoscopy (for patients
treated at the maximum tolerated dose [expanded cohort only])

- Pleural effusions or abdominal ascites are not considered biopsy-accessible
tissue

- No known new CNS metastases that have not been previously treated

- Performance status - Karnofsky 60-100%

- WBC ≥ 3,000/mm^3

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

- Platelet count ≥ 100,000/mm^3

- Bilirubin ≤ 1.5 mg/dL

- AST and ALT ≤ 3 times upper limit of normal (ULN) (5 times ULN if liver metastases
are present)

- Creatinine ≤ 1.5 mg/dL

- No history of cardiac arrhythmias

- No myocardial infarction within the past 12 months

- No active ischemic heart disease within the past 12 months

- No New York Heart Association class III-IV congestive heart failure or LVEF < 40% by
MUGA

- No history of uncontrolled cardiac dysrhythmia or dysrhthmias requiring medication

- No history of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation ≥ 3 beats in a row)

- No congenital long QT syndrome

- No left bundle branch block

- QTc < 450 msec (for male patients)

- QTc < 470 msec (for female patients)

- Not pregnant

- No nursing during and for 2 months after study participation

- Negative pregnancy test

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

- No serious or uncontrolled infection

- No history of serious allergic reaction to eggs
or egg products

- No other medical condition that would preclude study participation

- At least 3 weeks since prior immunotherapy

- No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)

- At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

- Prior irinotecan allowed

- No prior 17-N-allylamino-17-demethoxygeldanamycin (17-AAG)

- At least 2 weeks since prior non-myelosuppressive chemotherapy (at the discretion of
the principal investigator)

- At least 3 weeks since prior radiotherapy

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

- Recovered from all prior therapy

- At least 3 weeks since prior anticancer investigational therapeutic drugs

- More than 7 days since prior and no concurrent inducers, inhibitors, or modifiers of
CYP3A4, including any of the following:

- Fluconazole

- Itraconazole

- Ketoconazole

- Azithromycin

- Clarithromycin

- Erythromycin

- Troleandomycin

- Nifedipine

- Verapamil

- Diltiazem

- Nefazodone

- Cyclosporine

- Grapefruit juice (> 1 quart/day)

- Indinavir

- Nelfinavir

- Ritonavir

- Saquinavir

- Carbamazepine

- Phenobarbital

- Phenytoin

- Rifampin

- Hydrastis canadensis (goldenseal)

- Hypericum perforatum (St. John's wort)

- Uncaria tomentosa (cat's claw)

- Echinacea angustifolia root

- Trifolium pratense (wild cherry)

- Matricaria chamomila (chamomile)

- Glycyrrhiza glabra (licorice)

- Dillapiol

- Hypericin

- Naringenin

- No concurrent medications that would prolong QTc

- No concurrent vitamins, antioxidants, herbal preparations, or supplements

- Concurrent single daily multivitamin allowed

- No other concurrent anticancer therapy

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No other concurrent investigational medications