A Phase I Trial Of Gemcitabine, 17-Allylaminogeldanamycin (17-AAG) And Cisplatin In Advanced Solid Tumor Patients

Inclusion Criteria:

- Histologic proof of cancer that is now considered clinically unresectable

- Absolute neutrophil count (ANC) >= 1500/uL

- Platelets (PLT) >= 100,000/uL

- Total bilirubin =< 2 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) =< 2.5 x ULN

- Creatinine =< 1.5 x ULN

- Alkaline phosphatase =< 2 x ULN or =< 5 x ULN if liver involvement

- Hemoglobin (Hgb) >= 9.0 g/dL

- Ability to provide informed consent

- Willingness to return to Mayo Clinic Rochester for follow up

- Life expectancy >= 12 weeks

- Willingness to provide all biologic specimens as required by the protocol; this is
the mandatory translational research component

- Prior treatment with gemcitabine or cisplatin or both is allowed

- Patients who have had prior anthracycline must have a normal ejection fraction on
multi gated acquisition scan (MUGA)

- Women of childbearing potential only: negative serum pregnancy test done =< 7 days
prior to registration

Exclusion Criteria:

- Known standard therapy for the patient's disease that is potentially curative or
definitely capable of extending life expectancy

- ECOG performance status (PS) 2, 3 or 4

- Uncontrolled infection

- Any of the following prior therapies:

- Chemotherapy =< 4 weeks prior to study entry

- Mitomycin C/nitrosoureas =< 6 weeks prior to study entry

- Immunotherapy =< 4 weeks prior to study entry

- Biologic therapy =< 4 weeks prior to study entry

- Radiation therapy =< 4 weeks prior to study entry, or any radiation that
potentially included the heart in the field (e.g., mantle)

- Radiation to > 25% of bone marrow

- Radiopharmaceuticals

- Chest radiation

- Failure to fully recover from acute, reversible effects of prior chemotherapy
regardless of interval since last treatment

- Significant cardiac disease including:

- Heart failure that meets New York Heart Association classification III or IV

- History of myocardial infarction =< one year of study entry

- Uncontrolled dysrhythmias or requiring antiarrhythmic drugs, or

- Poorly controlled angina

- Active ischemic heart disease =< 12 months prior to study entry

- Congenital long QT syndrome

- Left bundle branch block

- Central nervous system (CNS) metastases or seizure disorder

- Any of the following:

- Pregnant women

- Nursing women

- Men or women of childbearing potential who are unwilling to employ adequate
contraception (condoms, diaphragm, injections, intrauterine device [IUD], or
abstinence, etc.) Note: Concurrent use of oral contraceptives is contraindicated

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational (utilized for a non-Food and Drug Administration
[FDA]-approved indication and in the context of a research investigation)

- History of serious allergic reactions to eggs

- Concurrent use of drugs known to be inhibitors of the 3A4 enzyme

- >= grade 2 peripheral neuropathy, as defined by the National Cancer Institute (NCI)
Common Toxicity Criteria (CTC) version 2.0

- Significant underlying pulmonary disease as manifested by requirement for oxygen or
pulmonary fibrosis on chest x-ray

- Use of concomitant medications that prolong or may prolong corrected QT interval
(QTc)

- History of serious ventricular arrhythmia (ventricular tachycardia [VT] or
ventricular fibrillation [VF], >= 3 beats in a row), QTc >= 450 msec for men and 470
msec for women, or left ventricular ejection fraction (LVEF) =< 40% by MUGA

- Patients with symptomatic pulmonary disease requiring medication including the
following: dyspnea, dyspnea on exertion, paroxysmal nocturnal dyspnea, oxygen
requirement and significant pulmonary disease, including chronic
obstructive/restrictive pulmonary disease; note: patients that meet the Medicare
criteria for home oxygen should be excluded from the protocol

- Patients with a prior history of cardiac or pulmonary toxicity after receiving
anthracyclines such as doxorubicin, daunorubicin, mitoxantrone, bleomycin or
carmustine (BCNU)

- Patients with greater or equal to grade 2 pulmonary or cardiac symptoms